subject:(chronic myeloid leukemia)

University of Adelaide

1. Hiwase, Devendra. Evaluation of anti-proliferative and pro-apoptotic effects of tyrosine kinase inhibitors on CML-CD34+ cells.

Degree: 2010, University of Adelaide

URL: http://hdl.handle.net/2440/65253

► Although imatinib (IM) has revolutionalised CML management, 30 to 40% patients fail IM therapy. Many of these patients can be rescued with second generation tyrosine… (more)

▼ Although imatinib (IM) has revolutionalised CML management, 30 to 40% patients fail IM therapy. Many of these patients can be rescued with second generation tyrosine kinase inhibitors (TKI), dasatinib, nilotinib and bosutinib. This research elucidates the dasatinib cellular transport pathways and its role in mediating dasatinib resistance. It also assesses dynamics of Bcr-Abl kinase inhibition and apoptosis in CML lines and CML-CD34+ progenitors. Lastly it addresses the role of cytokines in mediating TKI resistance and possible combination therapy to circumvent cytokine mediated TKI resistance. The organic cation transporter (OCT-1) mediates IM influx and low OCT-1 activity is a major contributor to suboptimal response in CML patients treated with IM. In the current study the relevance of OCT-1 activity and efflux pumps in determining intracellular concentration (IUR) of dasatinib were assessed. In contrast to IM, dasatinib cellular uptake is not significantly affected by OCT-1 activity, so that expression and function of OCT-1 is unlikely to affect response to dasatinib. Dasatinib is a substrate of efflux proteins, ABCB1 and ABCG2. Overexpression of these proteins can mediate dasatinib resistance. There is increasing evidence that nilotinib is an ABCB1 inhibitor. These different interactions of dasatinib and nilotinib with ABCB1 were exploited for combination therapy. Nilotinib increased 14CDasatinib IUR and had synergistic effect in inducing cell death in ABCB1 overexpressing cells. These data suggest that combinations of these two TKI can overcome ABCB1 mediated dasatinib resistance and may allow the use of lower concentrations of each drug. In contrast to IM, dasatinib cellular influx is predominantly passive and maximum intracellular concentration is achieved within a few minutes. This was further confirmed by the observation of maximum Bcr-Abl kinase inhibition within 30 minutes of culture with dasatinib. Despite reactivation of Bcr-Abl kinase within 30 minutes of drug washout, short-term (30 minutes) intense (>90%) Bcr-Abl kinase inhibition with dasatinib triggers apoptosis in CML cell lines. This is in contrast to the previously established paradigm that continuous kinase inhibition is required for optimal response to IM. These results were further supported by a recently published dasatinib dose optimisation study. Further work in this thesis demonstrated that although Bcr-Abl kinase reactivates within 30 minutes of drug washout, the prosurvival proteins Erk, AKT and STAT5 dephosphorylated rapidly while the apoptotic proteins remained phosphorylated. This differential degradation of prosurvival and apoptotic proteins might be responsible for a state of “oncogenic-shock”, as described by Sharma et al. Subsequent studies demonstrated that in the absence of cytokines, short-term intense Bcr-Abl kinase inhibition with therapeutically achievable concentration of dasatinib (100 nM dasatinib) eliminated 70 to 80% of CML-CD34+ progenitors. However, in the presence of cytokines despite >90% Bcr-Abl kinase … Advisors/Committee Members: Hughes, Timothy Peter (advisor), Kumar, Sharad (advisor), Vaz de Melo, Junia (advisor), White, Deborah (advisor), School of Medicine (school).

Subjects/Keywords: chronic myeloid leukemia; dasatinib; cytokines

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APA (6^th Edition):

Hiwase, D. (2010). Evaluation of anti-proliferative and pro-apoptotic effects of tyrosine kinase inhibitors on CML-CD34+ cells. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/65253

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Hiwase, Devendra. “Evaluation of anti-proliferative and pro-apoptotic effects of tyrosine kinase inhibitors on CML-CD34+ cells.” 2010. Thesis, University of Adelaide. Accessed April 14, 2021. http://hdl.handle.net/2440/65253.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Hiwase, Devendra. “Evaluation of anti-proliferative and pro-apoptotic effects of tyrosine kinase inhibitors on CML-CD34+ cells.” 2010. Web. 14 Apr 2021.

Vancouver:

Hiwase D. Evaluation of anti-proliferative and pro-apoptotic effects of tyrosine kinase inhibitors on CML-CD34+ cells. [Internet] [Thesis]. University of Adelaide; 2010. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2440/65253.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Hiwase D. Evaluation of anti-proliferative and pro-apoptotic effects of tyrosine kinase inhibitors on CML-CD34+ cells. [Thesis]. University of Adelaide; 2010. Available from: http://hdl.handle.net/2440/65253

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Hong Kong

2. Kwan, Tsz-ki. The detection of BCR-ABL kinase domain mutation in the management of chronic myeloid leukemia.

Degree: 2008, University of Hong Kong

URL: http://hdl.handle.net/10722/52028

Subjects/Keywords: Chronic myeloid leukemia.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kwan, T. (2008). The detection of BCR-ABL kinase domain mutation in the management of chronic myeloid leukemia. (Thesis). University of Hong Kong. Retrieved from http://hdl.handle.net/10722/52028

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Kwan, Tsz-ki. “The detection of BCR-ABL kinase domain mutation in the management of chronic myeloid leukemia.” 2008. Thesis, University of Hong Kong. Accessed April 14, 2021. http://hdl.handle.net/10722/52028.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Kwan, Tsz-ki. “The detection of BCR-ABL kinase domain mutation in the management of chronic myeloid leukemia.” 2008. Web. 14 Apr 2021.

Vancouver:

Kwan T. The detection of BCR-ABL kinase domain mutation in the management of chronic myeloid leukemia. [Internet] [Thesis]. University of Hong Kong; 2008. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/10722/52028.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Kwan T. The detection of BCR-ABL kinase domain mutation in the management of chronic myeloid leukemia. [Thesis]. University of Hong Kong; 2008. Available from: http://hdl.handle.net/10722/52028

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Lund

3. Hansen, Nils. Functional Modeling of Genes Upregulated in Chronic Myeloid Leukemia.

Degree: 2013, University of Lund

URL: https://lup.lub.lu.se/record/4143998 ; https://portal.research.lu.se/ws/files/3452298/4144000.pdf

► Chronic myeloid leukemia (CML) is caused by the transformation of a primitive hematopoietic cell by the BCR/ABL1 fusion gene that is formed through the chromosomal… (more)

▼ Chronic myeloid leukemia (CML) is caused by the transformation of a primitive hematopoietic cell by the BCR/ABL1 fusion gene that is formed through the chromosomal translocation t(9;22). CML is currently successfully treated with tyrosine kinase inhibitors targeting the ABL1 kinase domain. However, the CML stem cells are insensitive to this drug and a large fraction of patients will have relapse following discontinuation of the drug. Thus, improved therapeutic strategies are needed towards the ultimate goal of curing CML. In Article I, the functional role of supressor of cytokine signaling 2 (SOCS2) in CML and in normal hematopoiesis was investigated. Mice deficient for the Socs2 gene displayed normal steady-state hematopoiesis and hematopoietic stem cell (HSC) function. Transduction of bone marrow (BM) cells from Socs2-deficient mice with BCR/ABL1 and subsequent transplantation resulted in a CML-like disease indistuingishable from the disease in control mice, suggesting that SOCS2 is dispensible for normal hematopoiesis and CML pathogenesis. In Article II, global gene expression analysis and subsequent flow cytometric analysis of normal and CML BM cells showed that interleukin-1 receptor acessory protein (IL1RAP) was highly upregulated on the cell surface of CML cells, allowing prospective separation of candidate CML stem cells from normal hematopoietic stem cells. The use of a polyclonal IL1RAP antibody enabled antibody-dependent cellular cytotoxicity (ADCC) of CD34+CD38- CML cells in vitro. In Article III, the function of IL1RAP in normal hematopoeisis and in CML was investigated. Mice lacking Il1rap displayed lower myeloid steady-state cell counts. Overexpression of IL1RAP in cord blood cells, followed by transplantation into immunodeficient mice, resulted in increased levels of myelopoeisis. Finally, CD34+CD38- CML cells were found to respond strongly to IL1B stimulation in vitro. Together, the results suggest that IL1RAP is a promising target for novel therapeutic approaches in CML.

Subjects/Keywords: Medical Genetics; Chronic myeloid leukemia; SOCS2; IL1RAP; BCR/ABL1; leukemia models

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Hansen, N. (2013). Functional Modeling of Genes Upregulated in Chronic Myeloid Leukemia. (Doctoral Dissertation). University of Lund. Retrieved from https://lup.lub.lu.se/record/4143998 ; https://portal.research.lu.se/ws/files/3452298/4144000.pdf

Chicago Manual of Style (16^th Edition):

Hansen, Nils. “Functional Modeling of Genes Upregulated in Chronic Myeloid Leukemia.” 2013. Doctoral Dissertation, University of Lund. Accessed April 14, 2021. https://lup.lub.lu.se/record/4143998 ; https://portal.research.lu.se/ws/files/3452298/4144000.pdf.

MLA Handbook (7^th Edition):

Hansen, Nils. “Functional Modeling of Genes Upregulated in Chronic Myeloid Leukemia.” 2013. Web. 14 Apr 2021.

Vancouver:

Hansen N. Functional Modeling of Genes Upregulated in Chronic Myeloid Leukemia. [Internet] [Doctoral dissertation]. University of Lund; 2013. [cited 2021 Apr 14]. Available from: https://lup.lub.lu.se/record/4143998 ; https://portal.research.lu.se/ws/files/3452298/4144000.pdf.

Council of Science Editors:

Hansen N. Functional Modeling of Genes Upregulated in Chronic Myeloid Leukemia. [Doctoral Dissertation]. University of Lund; 2013. Available from: https://lup.lub.lu.se/record/4143998 ; https://portal.research.lu.se/ws/files/3452298/4144000.pdf

4. Grauers Wiktorin, Hanna. Redox reactions in cancer: impact and regulation.

Degree: 2018, University of Gothenburg / Göteborgs Universitet

URL: http://hdl.handle.net/2077/56884

► The reduction-oxidation (redox) reaction involves a change in the oxidation state of molecules where a molecule that donates an electron is oxidized and a molecule… (more)

▼ The reduction-oxidation (redox) reaction involves a change in the oxidation state of molecules where a molecule that donates an electron is oxidized and a molecule that accepts an electron is reduced. The NADPH oxidase of myeloid cells, NOX2, is a major source of oxidants in the form of reactive oxygen species (ROS), which are short-lived oxygen derivatives. NOX2-derived ROS have been ascribed a pivotal role in the elimination of pathogens and may be toxic also to host cells and tissues. ROS may also act as signaling molecules and thus regulate biological processes such as cell cycle proliferation, differentiation, cell death, blood vessel formation, and immunity. The purpose of this thesis was to contribute to the understanding of the impact and regulation of redox reactions in cancer with focus on the role of NOX2. The studies have comprised cells and animals that were genetically or pharmacologically deprived of NOX2 activity, and attempts were made to define the significance of the findings in a clinical setting. The results presented in paper I imply that ROS may inhibit the maturation of monocytes into antigen-presenting dendritic cells, which may favor tumor growth in vivo. Paper II reports that treatment of mice with the NOX2 inhibitor histamine dihydrochloride (HDC) resulted in reduced expansion and reduced immunosuppressive activity of myeloid-derived suppressor cells. Treatment of mice with HDC also improved the efficacy of checkpoint inhibitors to reduce the growth of murine lymphoma and colon cancer. The results of paper III suggest that HDC, by targeting NOX2-derived ROS, promotes the differentiation of acute myeloid leukemia (AML) cells in vitro and in vivo, thus implying that the intrinsic formation of ROS by AML cells contributes to their malignant features. In paper IV it is reported that functional NOX2 is relevant to the induction of chronic myeloid leukemia by murine BCR-ABL1+ cells. In conclusion, these results support that NOX2 is a conceivable therapeutic target in cancer.

Subjects/Keywords: Cancer; Immunotherapy; reactive oxygen species; NOX2; histamine dihydrochloride; myeloid-derived suppressor cells; checkpoint inhibition; acute myeloid leukemia; chronic myeloid leukemia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Grauers Wiktorin, H. (2018). Redox reactions in cancer: impact and regulation. (Thesis). University of Gothenburg / Göteborgs Universitet. Retrieved from http://hdl.handle.net/2077/56884

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Grauers Wiktorin, Hanna. “Redox reactions in cancer: impact and regulation.” 2018. Thesis, University of Gothenburg / Göteborgs Universitet. Accessed April 14, 2021. http://hdl.handle.net/2077/56884.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Grauers Wiktorin, Hanna. “Redox reactions in cancer: impact and regulation.” 2018. Web. 14 Apr 2021.

Vancouver:

Grauers Wiktorin H. Redox reactions in cancer: impact and regulation. [Internet] [Thesis]. University of Gothenburg / Göteborgs Universitet; 2018. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2077/56884.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Grauers Wiktorin H. Redox reactions in cancer: impact and regulation. [Thesis]. University of Gothenburg / Göteborgs Universitet; 2018. Available from: http://hdl.handle.net/2077/56884

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

NSYSU

5. Chang Chien, Jung-Jung. Effect of quinacrine on Bcl-xL and Bcl-2 expression in human leukemia K562 cells.

Degree: Master, Institute of Biomedical Sciences, 2014, NSYSU

URL: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0617114-144613

► Quinacrine, also known as mepacrine, is a drug applied on anti-protozoal and anti-rheumatic therapy. Moreover, quinacrine functioned as an intrapleural sclerosing agent as well. Although… (more)

Subjects/Keywords: Quinacrine; Chronic myeloid leukemia; Bcl-xL; Bcl-2; apoptosis

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Chang Chien, J. (2014). Effect of quinacrine on Bcl-xL and Bcl-2 expression in human leukemia K562 cells. (Thesis). NSYSU. Retrieved from http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0617114-144613

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Chang Chien, Jung-Jung. “Effect of quinacrine on Bcl-xL and Bcl-2 expression in human leukemia K562 cells.” 2014. Thesis, NSYSU. Accessed April 14, 2021. http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0617114-144613.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Chang Chien, Jung-Jung. “Effect of quinacrine on Bcl-xL and Bcl-2 expression in human leukemia K562 cells.” 2014. Web. 14 Apr 2021.

Vancouver:

Chang Chien J. Effect of quinacrine on Bcl-xL and Bcl-2 expression in human leukemia K562 cells. [Internet] [Thesis]. NSYSU; 2014. [cited 2021 Apr 14]. Available from: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0617114-144613.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Chang Chien J. Effect of quinacrine on Bcl-xL and Bcl-2 expression in human leukemia K562 cells. [Thesis]. NSYSU; 2014. Available from: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0617114-144613

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Temple University

6. Maifrede, Silvia. EGR-1 TUMOR SUPPRESSOR IN BCR-ABL DRIVEN LEUKEMIA.

Degree: PhD, 2015, Temple University

URL: http://digital.library.temple.edu/u?/p245801coll10,321048

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Molecular Biology and Genetics

Chronic Myelogenous Leukemia (CML) is a hematological disease originated with a chromosomal translocation t(9;22)(q34;q11) in a pluripotent hematopoietic stem cell. CML… (more)

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Molecular Biology and Genetics

Chronic Myelogenous Leukemia (CML) is a hematological disease originated with a chromosomal translocation t(9;22)(q34;q11) in a pluripotent hematopoietic stem cell. CML typically evolves in 3 different clinical phases: chronic and accelerated phases, and blast crisis. Disease progression is associated with the acquisition of secondary mutations that can be of very diverse origins, including inactivation of tumor suppressor genes, as well as inhibition of differentiation, DNA repair and telomere maintenance. While current therapies are very often successful, the remaining issues of resistance and the fact that therapy will not cure CML make it important that new therapy capable of effectively curing it be developed. The early growth response-1 (Egr-1) gene is a zinc-finger transcription factor localized to the human chromosome 5. Egr-1 belongs to a family of early response genes whose expression is rapidly stimulated by growth factors, hormones and neurotransmitters. In addition, Egr-1 is a myeloid differentiation primary response (MYD) gene, and is a positive regulator of terminal myeloid differentiation that potentiates macrophage differentiation. It also has been shown that Egr-1 plays a role in the development, growth control and survival of several cell types, such as T cells, B cells, and neuronal cells in addition to myeloid cells. There is a large amount of evidence consistent with Egr-1 behaving as a tumor suppressor in hematopoietic cells, both in vivo & in vitro, in both humans & mice, making it a prime candidate for a role in CML. In this study we asked if Egr-1 would behave as a tumor suppressor in CML. To answer that we investigated the function of Egr-1 in BCR-ABL driven leukemia using a mouse m bone marrow transplantation (BMT) model. We observe that loss of Egr-1 accelerates the onset of BCR-ABL driven CML. Furthermore, through Facs analysis we showed that most animals developed myeloid leukemia, determined by the observation that the majority of GFP+ cells in the BM were positive for Gr-1 and negative for B220. Interestingly a small cohort of mice developed B-cell acute lymphoid leukemia (B-ALL); this included both WT BCR-ABL and Egr-1 KO BCR-ABL BM-transplanted groups. In addition, we demonstrated that the loss of Egr-1 caused a more aggressive leukemia, which resulted not only in more rapid onset of disease but also greater enlargement of spleen and liver, as well as a tendency to more aggressive lung infiltration of leukemic cells. We also showed that decreased apoptosis, increased proliferation rates and resulting increased viability are consistent with, and probably contribute to, the increased leukemic potential of Egr-1 KO BCR-ABL BM. In addition, we demonstrated that Egr-1 expression was downregulated in BCR-ABL expressing BM cells in vitro, and in spleens of transplanted leukemic mice. Moreover, a very interesting observation, consistent with the rapid onset and aggression of disease, was that the bone marrow of leukemic mice caused by Egr-1 KO BCR-ABL BM…

Advisors/Committee Members: Hoffman, Barbara;, Liebermann, Dan A., Grana-Amat, Xavier, Engel, Nora, Shore, Scott K., Sykes, Stephen M.;.

Subjects/Keywords: Molecular biology;

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Maifrede, S. (2015). EGR-1 TUMOR SUPPRESSOR IN BCR-ABL DRIVEN LEUKEMIA. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,321048

Chicago Manual of Style (16^th Edition):

Maifrede, Silvia. “EGR-1 TUMOR SUPPRESSOR IN BCR-ABL DRIVEN LEUKEMIA.” 2015. Doctoral Dissertation, Temple University. Accessed April 14, 2021. http://digital.library.temple.edu/u?/p245801coll10,321048.

MLA Handbook (7^th Edition):

Maifrede, Silvia. “EGR-1 TUMOR SUPPRESSOR IN BCR-ABL DRIVEN LEUKEMIA.” 2015. Web. 14 Apr 2021.

Vancouver:

Maifrede S. EGR-1 TUMOR SUPPRESSOR IN BCR-ABL DRIVEN LEUKEMIA. [Internet] [Doctoral dissertation]. Temple University; 2015. [cited 2021 Apr 14]. Available from: http://digital.library.temple.edu/u?/p245801coll10,321048.

Council of Science Editors:

Maifrede S. EGR-1 TUMOR SUPPRESSOR IN BCR-ABL DRIVEN LEUKEMIA. [Doctoral Dissertation]. Temple University; 2015. Available from: http://digital.library.temple.edu/u?/p245801coll10,321048

Rhodes University

7. Kibet, Caleb Kipkurui. Analysis of transcription factor binding specificity using ChIP-seq data.

Degree: MS, Faculty of Science, Biochemistry, Microbiology and Biotechnology, 2014, Rhodes University

URL: http://hdl.handle.net/10962/d1013131

► Transcription factors (TFs) are key regulators of gene expression whose failure has been implicated in many diseases, including cancer. They bind at various sites at… (more)

▼ Transcription factors (TFs) are key regulators of gene expression whose failure has been implicated in many diseases, including cancer. They bind at various sites at different specificity depending on the prevailing cellular conditions, disease, development stage or environmental conditions of the cell. TF binding specificity is how well a TF distinguishes functional sites from potential non-functional sites to form a useful regulatory network. Owing to its role in diseases, various techniques have been used to determine TF binding specificity in vitro and in vivo, including chromatin immuno-precipitation followed by massively parallel sequencing (ChIP-seq). ChIP-seq is an in vivo technique that considers how the chromatin landscape affects TF binding. Motif enrichment analysis (MEA) tools are used to identify motifs that are over-represented in ChIP-seq peak regions. One such tool, CentriMo, finds over-represented motifs at the center since peak calling software are biased to declaring binding regions centered at the TF binding site. In this study, we investigate the use of CentriMo and other MEA tools to determine the difference in motif enrichment attributed presence of Chronic Myeloid leukemia (CML)), treatment with Interferon (IFN) and Dexamethasone (DEX) compared to control based on Fisher’s exact test; using uniform peaks ChIP-seq data generated by the ENCODE consortium. CentriMo proved to be capable. We observed differential motif enrichment of TFs with tumor promoter activity: YY1, CEBPA, Egr1, Cmyc family, Gata1 and JunD in K562 while Stat1, Irf1, and Runx1 in Gm12878. Enrichment of CTCF in Gm12878 with YY1 as the immuno-precipitated (ChIP-ed) factor and the presence of significant spacing (SpaMo analysis) of CTCF and YY1 in Gm12878 but not in K562 could show that CTCF, as a repressor, helps in maintaining the required YY1 level in a normal cell line. IFN might reduce Cmyc and the Jun family of TFs binding via the repressive action of CTCF and E2f2. We also show that the concentration of DEX treatment affects motif enrichment with 50nm being an optimum concentration for Gr binding by maintaining open chromatin via AP1 TF. This study has demonstrated the usefulness of CentriMo for TF binding specificity analysis. Advisors/Committee Members: Machanick, Philip.

Subjects/Keywords: Transcription factors; Chronic myeloid leukemia; Antioncogenes; Cancer cells – Growth – Regulation

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kibet, C. K. (2014). Analysis of transcription factor binding specificity using ChIP-seq data. (Masters Thesis). Rhodes University. Retrieved from http://hdl.handle.net/10962/d1013131

Chicago Manual of Style (16^th Edition):

Kibet, Caleb Kipkurui. “Analysis of transcription factor binding specificity using ChIP-seq data.” 2014. Masters Thesis, Rhodes University. Accessed April 14, 2021. http://hdl.handle.net/10962/d1013131.

MLA Handbook (7^th Edition):

Kibet, Caleb Kipkurui. “Analysis of transcription factor binding specificity using ChIP-seq data.” 2014. Web. 14 Apr 2021.

Vancouver:

Kibet CK. Analysis of transcription factor binding specificity using ChIP-seq data. [Internet] [Masters thesis]. Rhodes University; 2014. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/10962/d1013131.

Council of Science Editors:

Kibet CK. Analysis of transcription factor binding specificity using ChIP-seq data. [Masters Thesis]. Rhodes University; 2014. Available from: http://hdl.handle.net/10962/d1013131

8. Saliba, Jessica. Activité anti-tumorale de l'EAPB0503, un nouveau composé imidazoquinoxaline, sur la Leucémie Myéloïde Chronique : Anti-tumoral properties of EAPB0503, a new imidazoquinoxaline compound, in Chronic Myeloid Leukemia.

Degree: Docteur es, Biologie Santé, 2013, Université Montpellier I

URL: http://www.theses.fr/2013MON13520

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La leucémie myéloïde chronique (LMC) est une maladie myéloproliférative, résultant d'une translocation réciproque entre les chromosomes 9 et 22, donnant naissance à une kinase de… (more)

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La leucémie myéloïde chronique (LMC) est une maladie myéloproliférative, résultant d'une translocation réciproque entre les chromosomes 9 et 22, donnant naissance à une kinase de fusion à activité continue, la BCR-ABL. Les inhibiteurs de la tyrosine kinase (ITK) sont le traitement de choix de la LMC, mais ces inhibiteurs n'offrent pas de cure radicale aux patients, qui, une fois le traitement interrompu, présentent une rechute et une exacerbation de leur condition. En plus, les patients peuvent développer une résistance ou une intolérance aux ITK, d'où la nécessité de nouvelles modalités thérapeutiques. Les imidazoquinoxalines sont de nouveaux composés à visée anticancéreuse, dont la structure est basée sur celle de l'imiquimod, un immunomodulateur connu. EAPB0203, un composé du groupe des imidazo[1,2-α]quinoxalines, a fait preuve d'un pouvoir anticancéreux sur des cellules de mélanome, in vitro et in vivo, ainsi que sur des cellules de leucémie liée au virus HTLV-1, in vitro. EAPB0503 est un composé de la même famille, à pouvoir environ 10 fois supérieur à celui de l'EAPB0203 sur les cellules de mélanome. Dans le cadre de ce projet de thèse, l'activité de l'EAPB0203 a été comparée à celle de l'EAPB0503, et leur effet sur la prolifération de trois lignées cellulaires de LMC a confirmé que l'EAPB0503 est plus efficace que l'EAPB0203. Pour ce, l'EAPB0503 a été adopté pour la suite des expérimentations que nous avons entreprises dans le but de caractériser le mécanisme d'action par lequel ce composé inhibe la croissance cellulaire. Les CI50 de l'EAPB0503 ont été déterminées pour chacune des trois lignées, et adoptées tout au long du travail. On a démontré que l'EAPB0503 provoque un arrêt du cycle cellulaire en PréG0 (accumulation de cellules apoptotiques) et en G2/M. Une nette augmentation du niveau de phosphorylation de l'histone-3 suggère un arrêt des cellules en début de mitose. Cet arrêt du cycle cellulaire s'accompagne d'une diminution du potentiel membranaire mitochondrial, d'une activation modérée du cytochrome c et du clivage de PARP (suggérant l'implication de caspases). On a également démontré que l'EAPB0503 induit l'apoptose comme le montre la fragmentation de l'ADN. Des résultats préliminaires proposent aussi une stabilisation de la protéine pro-apoptotique, bax, et une diminution du niveau de la protéine anti-apoptotique Bcl-2, augmentant ainsi le rapport Bax/Bcl-2 et renversant ainsi l'équilibre du côté apoptotique. En plus, EAPB0503 a potentialisé l'effet de l'imatinib (le premier ITK), et, à deux, ces deux agents ont eu un effet synergique sur la croissance des cellules de LMC. Il a été également très intéressant de montrer que l'EAPB0503 dégrade l'oncoprotéine, BCR-ABL, dans les cellules sensibles et résistantes à l'imatinib. Ensemble, ces résultats suggèrent un effet prometteur de l'EAPB0503 sur la LMC, en monothérapie ou en association avec les ITK.

Chronic myeloid leukemia (CML) is a myeloproliferative disorder that originates in a reciprocal translocation, resulting in the Philadelphia chromosome…

Advisors/Committee Members: Bonnet, Pierre-Antoine (thesis director), Nasr, Rihab (thesis director).

Subjects/Keywords: Imidazoquinoxalines; Leucemie myeloide chronique; Apoptose; Imidazoquinoxalines; Chronic Myeloid Leukemia; Apoptosis; 616

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Saliba, J. (2013). Activité anti-tumorale de l'EAPB0503, un nouveau composé imidazoquinoxaline, sur la Leucémie Myéloïde Chronique : Anti-tumoral properties of EAPB0503, a new imidazoquinoxaline compound, in Chronic Myeloid Leukemia. (Doctoral Dissertation). Université Montpellier I. Retrieved from http://www.theses.fr/2013MON13520

Chicago Manual of Style (16^th Edition):

Saliba, Jessica. “Activité anti-tumorale de l'EAPB0503, un nouveau composé imidazoquinoxaline, sur la Leucémie Myéloïde Chronique : Anti-tumoral properties of EAPB0503, a new imidazoquinoxaline compound, in Chronic Myeloid Leukemia.” 2013. Doctoral Dissertation, Université Montpellier I. Accessed April 14, 2021. http://www.theses.fr/2013MON13520.

MLA Handbook (7^th Edition):

Saliba, Jessica. “Activité anti-tumorale de l'EAPB0503, un nouveau composé imidazoquinoxaline, sur la Leucémie Myéloïde Chronique : Anti-tumoral properties of EAPB0503, a new imidazoquinoxaline compound, in Chronic Myeloid Leukemia.” 2013. Web. 14 Apr 2021.

Vancouver:

Saliba J. Activité anti-tumorale de l'EAPB0503, un nouveau composé imidazoquinoxaline, sur la Leucémie Myéloïde Chronique : Anti-tumoral properties of EAPB0503, a new imidazoquinoxaline compound, in Chronic Myeloid Leukemia. [Internet] [Doctoral dissertation]. Université Montpellier I; 2013. [cited 2021 Apr 14]. Available from: http://www.theses.fr/2013MON13520.

Council of Science Editors:

Saliba J. Activité anti-tumorale de l'EAPB0503, un nouveau composé imidazoquinoxaline, sur la Leucémie Myéloïde Chronique : Anti-tumoral properties of EAPB0503, a new imidazoquinoxaline compound, in Chronic Myeloid Leukemia. [Doctoral Dissertation]. Université Montpellier I; 2013. Available from: http://www.theses.fr/2013MON13520

Brandeis University

9. Hollander, Klarissa. Understanding the Interplay Between Different Regulatory Features of Abl Kinase.

Degree: 2020, Brandeis University

URL: http://hdl.handle.net/10192/37525

► Abl is a member of the non-receptor tyrosine kinase family, a group of enzymes responsible for propagation of cell signals, including those responsible for cell… (more)

Subjects/Keywords: Kinase; Regulation; Tyrosine Kinase; Abl; Myristoylation; Phosphorylation; Chronic Myeloid Leukemia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Hollander, K. (2020). Understanding the Interplay Between Different Regulatory Features of Abl Kinase. (Thesis). Brandeis University. Retrieved from http://hdl.handle.net/10192/37525

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Hollander, Klarissa. “Understanding the Interplay Between Different Regulatory Features of Abl Kinase.” 2020. Thesis, Brandeis University. Accessed April 14, 2021. http://hdl.handle.net/10192/37525.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Hollander, Klarissa. “Understanding the Interplay Between Different Regulatory Features of Abl Kinase.” 2020. Web. 14 Apr 2021.

Vancouver:

Hollander K. Understanding the Interplay Between Different Regulatory Features of Abl Kinase. [Internet] [Thesis]. Brandeis University; 2020. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/10192/37525.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Hollander K. Understanding the Interplay Between Different Regulatory Features of Abl Kinase. [Thesis]. Brandeis University; 2020. Available from: http://hdl.handle.net/10192/37525

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universidade Estadual de Campinas

10. Carvalho, Fernanda de Cássia Frasson, 1978-. Avaliação da expressão dos genes TARP, ncTNFAIP8, IFNG, FASLG e AKT1 em pacientes com leucemia mieloide crônica resistentes ao imatinibe tratados com dasatinibe.

Degree: Faculdade de Ciências Médicas; Programa de Pós-Graduação em Clínica Médica, 2017, Universidade Estadual de Campinas

URL: http://repositorio.unicamp.br/jspui/handle/REPOSIP/333856

►

Orientador: Katia Borgia Barbosa Pagnano

Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas

Made available in DSpace on 2019-05-06T15:34:31Z (GMT). No. of… (more)

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Orientador: Katia Borgia Barbosa Pagnano

Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas

Made available in DSpace on 2019-05-06T15:34:31Z (GMT). No. of bitstreams: 1 Carvalho_FernandaDeCassiaFrasson_M.pdf: 3711332 bytes, checksum: 8506ec9808219dfb0f6ca67583f0cb37 (MD5) Previous issue date: 2017

Resumo: A Leucemia Mieloide Crônica (LMC) é caracterizada pela presença do cromossomo Filadélfia (Ph), que resulta no gene de fusão BCR-ABL, cujo produto possui atividade tirosinoquinase aumentada. O tratamento da LMC é realizado com inibidores de tirosinoquinase (TKI). Apesar do aumento de sobrevida dos pacientes tratados com imatinibe, alguns pacientes apresentam resistência ou intolerância ao tratamento, sendo necessário a troca para um TKI de segunda geração. Os mecanismos de resistência são multifatoriais. Um trabalho anterior do nosso grupo identificou diversos genes e RNAs longos não codificantes diferencialmente expressos em pacientes responsivos e não responsivos ao dasatinibe, entre eles os genes TARP, ncTNFAIP8, IFNG, FASLG e AKT1. O objetivo desse trabalho foi avaliar através de PCR em tempo real a expressão dos genes TARP, ncTNFAIP8, IFNG, FASLG e AKT1 em pacientes com LMC ao diagnóstico, em pacientes tratados com dasatinibe ou imatinibe (resistentes e responsivos) e correlacionar com o escore de Sokal, sobrevida global, livre de progressão e livre de eventos. Dentre os achados mais significativos, o gene TARP foi hiperexpresso nos pacientes com LMC ao diagnóstico em relação ao grupo controle e também em pacientes com LMC pós dasatinibe (responsivos). FASLG foi hiperexpresso no grupo controle em relação aos pacientes com LMC ao diagnóstico e nos pacientes com LMC pós dasatinibe (responsivos e resistentes) em relação aos pacientes ao diagnóstico. TARP foi hiperexpresso nos pacientes com LMC ao diagnóstico e pós imatinibe em relação ao grupo controle e hiperexpresso nos pacientes com Sokal alto risco. FASLG apresentou hiperexpressão no grupo controle e nos pacientes com LMC pós imatinibe (responsivos e resistentes) em relação aos pacientes com LMC ao diagnóstico. Não houve alterações significativas na SG, SLP e SLE dos pacientes tratados com imatinibe de acordo com a expressão dos genes TARP, AKT1, IFNG, ncTNFFAIP8 e FASLG. Observou-se uma correlação positiva entre a expressão do BCR-ABL e o índice de Sokal. Esses achados sugerem que esses genes possam ter papel na fisiopatologia e em mecanismos de resistência na LMC, justificando futuros estudos

Chronic Myeloid Leukemia (CML) is characterized by the presence of Philadelphia chromosome (Ph), which results in the BCR-ABL fusion gene, whose product has increased tyrosine kinase activity. Tyrosine kinase inhibitors (TKIs) are used for CML treatment. Despite the increased survival of patients treated with imatinib, some patients develop resistance or treatment intolerance, requiring a switch to a second-generation TKI. Resistance mechanisms are multifactorial. A previous study from our group identified several…

Advisors/Committee Members: UNIVERSIDADE ESTADUAL DE CAMPINAS, Pagnano, Katia Borgia Barbosa, Bendit, Israel, Traina, Fabiola.

Subjects/Keywords: Leucemia mielóide crônica; Imatinibe; Dasatinibe; Chronic myeloid leukemia; Imatinib; Dasatinib

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Carvalho, Fernanda de Cássia Frasson, 1. (2017). Avaliação da expressão dos genes TARP, ncTNFAIP8, IFNG, FASLG e AKT1 em pacientes com leucemia mieloide crônica resistentes ao imatinibe tratados com dasatinibe. (Masters Thesis). Universidade Estadual de Campinas. Retrieved from http://repositorio.unicamp.br/jspui/handle/REPOSIP/333856

Chicago Manual of Style (16^th Edition):

Carvalho, Fernanda de Cássia Frasson, 1978-. “Avaliação da expressão dos genes TARP, ncTNFAIP8, IFNG, FASLG e AKT1 em pacientes com leucemia mieloide crônica resistentes ao imatinibe tratados com dasatinibe.” 2017. Masters Thesis, Universidade Estadual de Campinas. Accessed April 14, 2021. http://repositorio.unicamp.br/jspui/handle/REPOSIP/333856.

MLA Handbook (7^th Edition):

Carvalho, Fernanda de Cássia Frasson, 1978-. “Avaliação da expressão dos genes TARP, ncTNFAIP8, IFNG, FASLG e AKT1 em pacientes com leucemia mieloide crônica resistentes ao imatinibe tratados com dasatinibe.” 2017. Web. 14 Apr 2021.

Vancouver:

Carvalho, Fernanda de Cássia Frasson 1. Avaliação da expressão dos genes TARP, ncTNFAIP8, IFNG, FASLG e AKT1 em pacientes com leucemia mieloide crônica resistentes ao imatinibe tratados com dasatinibe. [Internet] [Masters thesis]. Universidade Estadual de Campinas; 2017. [cited 2021 Apr 14]. Available from: http://repositorio.unicamp.br/jspui/handle/REPOSIP/333856.

Council of Science Editors:

Carvalho, Fernanda de Cássia Frasson 1. Avaliação da expressão dos genes TARP, ncTNFAIP8, IFNG, FASLG e AKT1 em pacientes com leucemia mieloide crônica resistentes ao imatinibe tratados com dasatinibe. [Masters Thesis]. Universidade Estadual de Campinas; 2017. Available from: http://repositorio.unicamp.br/jspui/handle/REPOSIP/333856

Universidade Estadual de Campinas

11. Mascarenhas, Cintia do Couto, 1982-. Identificação e investigação de genes diferencialmente expressos entre pacientes com leucemia mielóide crônica e indivíduos controle.

Degree: Faculdade de Ciências Médicas; Programa de Pós-Graduação em Clínica Médica, 2013, Universidade Estadual de Campinas

URL: MASCARENHAS, Cintia do Couto. Identificação e investigação de genes diferencialmente expressos entre pacientes com leucemia mielóide crônica e indivíduos controle. 2013. 178 p. Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Campinas, SP. Disponível em: <http://www.repositorio.unicamp.br/handle/REPOSIP/308645>. Acesso em: 23 ago. 2018. ; http://repositorio.unicamp.br/jspui/handle/REPOSIP/308645

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Orientadores: Carmino Antonio de Souza, Fernando Ferreira Costa

Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas

Made available in DSpace on 2018-08-23T11:16:23Z… (more)

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Orientadores: Carmino Antonio de Souza, Fernando Ferreira Costa

Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas

Made available in DSpace on 2018-08-23T11:16:23Z (GMT). No. of bitstreams: 1 Mascarenhas_CintiadoCouto_D.pdf: 4558328 bytes, checksum: f219d85bc4e15d72a39a7d3242be9ffb (MD5) Previous issue date: 2013

Resumo: A elucidação dos mecanismos moleculares envolvidos na fisiopatologia e tratamento das doenças hematológicas, bem como no entendimento do perfil de expressão gênica das linhagens celulares leucêmicas, tem sido objeto de numerosas investigações. Com o uso da técnica SSH (Subtractive Supression Hybridization ou Biblioteca Subtrativa Supressiva) foi possível identificar importantes genes que se encontram diferencialmente expressos em granulócitos de pacientes com Leucemia Mielóide Crônica e indivíduos controle. Foram encontrados 39 genes superexpressos e 173 com expressão diminuída em células de LMC. Ao relacionar esses genes com vias metabólicas que estão reguladas positiva (expressão aumentada) ou negativamente (expressão diminuída) nessa doença, verificou-se que a maioria dos genes estavam relacionados com a regulação de NF-kB, AKT, o Interferon e a IL-4 em células de controle. Entre os genes superexpressos encontrados na LMC, foi observado o SEPT5, RUNX1, MIER1, KPNA6 e FLT3, enquanto PAN3, TOB1 e ITCH estavam com expressão diminuída nessa doença em comparação com indivíduos controle. O TOB1 se mostrou promissor, uma vez que é um gene supressor tumoral, pode estar envolvido na proliferação de células leucêmicas e interage com vários outros genes encontrados neste estudo. Assim, devido à grande heterogeneidade de funções relacionadas com a expressão desse gene, foi investigada a relação entre a expressão de mRNA e as respostas aos ITK's na LMC. A avaliação foi realizada por PCR em tempo real em doentes com CCgR, PCgR, MINCgR e NOCgR após tratamento com TKI's e os resultados foram comparados com a expressão em granulócitos de indivíduos controle, observando que os pacientes NOCgR têm uma expressão de TOB1 significativamente inferior em comparação com doadores saudáveis e pacientes que alcançaram RCgC. Ao comparar pacientes não resistentes e resistentes a diferença foi significativa. Esses resultados sugerem que a expressão diminuída de TOB1 em pacientes NOCgR pode ser indicativo de desregulação da apoptose e de vias de sinalização importantes nessa doença incluindo a via da AKT, conduzindo assim a resistência a ITK's nesses pacientes. Outro objetivo deste trabalho foi caracterizar a função dos genes TOB1 e SEPT5 nos processos celulares e vias de sinalização de apoptose, proliferação, migração e ciclo celular em linhagens celulares leucêmicas. Ao realizar o silenciamento desses genes (utilizando partículas lentivirais) notou-se que o silenciamento de TOB1, como já descrito na literatura em outras doenças, interfere na proliferação celular, clonogenicidade, apoptose, ciclo celular e expressão de proteínas importantes da cascata de sinalização, o que salienta…

Advisors/Committee Members: UNIVERSIDADE ESTADUAL DE CAMPINAS, Costa, Fernando Ferreira, 1950-, Souza, Carmino Antonio de, 1951-, Aranha, Francisco Jose Penteado, Lima, Carmen Silvia Passos, Melo, Monika Conchon Ribeiro de, Chauffaille, Maria de Lourdes Lopes Ferrari.

Subjects/Keywords: Leucemia mielóide crônica; Expressão gênica; Chronic myeloid leukemia; Gene expression

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Mascarenhas, Cintia do Couto, 1. (2013). Identificação e investigação de genes diferencialmente expressos entre pacientes com leucemia mielóide crônica e indivíduos controle. (Doctoral Dissertation). Universidade Estadual de Campinas. Retrieved from MASCARENHAS, Cintia do Couto. Identificação e investigação de genes diferencialmente expressos entre pacientes com leucemia mielóide crônica e indivíduos controle. 2013. 178 p. Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Campinas, SP. Disponível em: <http://www.repositorio.unicamp.br/handle/REPOSIP/308645>. Acesso em: 23 ago. 2018. ; http://repositorio.unicamp.br/jspui/handle/REPOSIP/308645

Chicago Manual of Style (16^th Edition):

Mascarenhas, Cintia do Couto, 1982-. “Identificação e investigação de genes diferencialmente expressos entre pacientes com leucemia mielóide crônica e indivíduos controle.” 2013. Doctoral Dissertation, Universidade Estadual de Campinas. Accessed April 14, 2021. MASCARENHAS, Cintia do Couto. Identificação e investigação de genes diferencialmente expressos entre pacientes com leucemia mielóide crônica e indivíduos controle. 2013. 178 p. Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Campinas, SP. Disponível em: <http://www.repositorio.unicamp.br/handle/REPOSIP/308645>. Acesso em: 23 ago. 2018. ; http://repositorio.unicamp.br/jspui/handle/REPOSIP/308645.

MLA Handbook (7^th Edition):

Mascarenhas, Cintia do Couto, 1982-. “Identificação e investigação de genes diferencialmente expressos entre pacientes com leucemia mielóide crônica e indivíduos controle.” 2013. Web. 14 Apr 2021.

Vancouver:

Mascarenhas, Cintia do Couto 1. Identificação e investigação de genes diferencialmente expressos entre pacientes com leucemia mielóide crônica e indivíduos controle. [Internet] [Doctoral dissertation]. Universidade Estadual de Campinas; 2013. [cited 2021 Apr 14]. Available from: MASCARENHAS, Cintia do Couto. Identificação e investigação de genes diferencialmente expressos entre pacientes com leucemia mielóide crônica e indivíduos controle. 2013. 178 p. Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Campinas, SP. Disponível em: <http://www.repositorio.unicamp.br/handle/REPOSIP/308645>. Acesso em: 23 ago. 2018. ; http://repositorio.unicamp.br/jspui/handle/REPOSIP/308645.

Council of Science Editors:

Mascarenhas, Cintia do Couto 1. Identificação e investigação de genes diferencialmente expressos entre pacientes com leucemia mielóide crônica e indivíduos controle. [Doctoral Dissertation]. Universidade Estadual de Campinas; 2013. Available from: MASCARENHAS, Cintia do Couto. Identificação e investigação de genes diferencialmente expressos entre pacientes com leucemia mielóide crônica e indivíduos controle. 2013. 178 p. Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Campinas, SP. Disponível em: <http://www.repositorio.unicamp.br/handle/REPOSIP/308645>. Acesso em: 23 ago. 2018. ; http://repositorio.unicamp.br/jspui/handle/REPOSIP/308645

Universidade do Minho

12. Machado, Fátima Alexandra Meira. Development of a liposomal formulation for peptide delivery to serve as vaccine against chronic myeloid leukemia .

Degree: 2013, Universidade do Minho

URL: http://hdl.handle.net/1822/29422

► The main goal of this work was to characterize and explore the potential of Dioctadecyldimethylammonium Chloride (DODAC) / Monoolein (MO) liposomes in a 1:2 proportion… (more)

Subjects/Keywords: DODAC/MO (1:2); Chronic myeloid leukemia; BCR-ABL; Vaccines; Leucemia mielóide crónica; Vacinas

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Machado, F. A. M. (2013). Development of a liposomal formulation for peptide delivery to serve as vaccine against chronic myeloid leukemia . (Masters Thesis). Universidade do Minho. Retrieved from http://hdl.handle.net/1822/29422

Chicago Manual of Style (16^th Edition):

Machado, Fátima Alexandra Meira. “Development of a liposomal formulation for peptide delivery to serve as vaccine against chronic myeloid leukemia .” 2013. Masters Thesis, Universidade do Minho. Accessed April 14, 2021. http://hdl.handle.net/1822/29422.

MLA Handbook (7^th Edition):

Machado, Fátima Alexandra Meira. “Development of a liposomal formulation for peptide delivery to serve as vaccine against chronic myeloid leukemia .” 2013. Web. 14 Apr 2021.

Vancouver:

Machado FAM. Development of a liposomal formulation for peptide delivery to serve as vaccine against chronic myeloid leukemia . [Internet] [Masters thesis]. Universidade do Minho; 2013. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/1822/29422.

Council of Science Editors:

Machado FAM. Development of a liposomal formulation for peptide delivery to serve as vaccine against chronic myeloid leukemia . [Masters Thesis]. Universidade do Minho; 2013. Available from: http://hdl.handle.net/1822/29422

Temple University

13. Morales, Kimberly. RAD52 DNA Binding Activity Can Be Targeted to Eliminate CML Stem Cells.

Degree: PhD, 2012, Temple University

URL: http://digital.library.temple.edu/u?/p245801coll10,190030

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Biology

BCR-ABL1 transforms hematopoietic stem cells into leukemia stem cells (LSCs) to induce chronic myeloid leukemia in chronic phase. Expression of BCR-ABL1 stimulates production of… (more)

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Biology

BCR-ABL1 transforms hematopoietic stem cells into leukemia stem cells (LSCs) to induce chronic myeloid leukemia in chronic phase. Expression of BCR-ABL1 stimulates production of elevated levels of reactive oxygen species (ROS), which induce oxidative DNA damage. CML cells accumulate excessive amounts of ROS-induced DNA damage which can be converted to potentially lethal DNA double strand breaks (DSBs). BCR-ABL1 stimulates enhanced Rad51-mediated DSB repair by the homologous recombination repair (HRR) pathway. In these studies we show BCR-ABL1-transformed cells depend on Rad52-mediated HRR to promote repair of ROS-induced DSBs and that this activity is dependent on Rad52 binding to single-stranded DNA (ssDNA). Our results show in the absence of Rad52, BCR-ABL1-positive hematopoietic cells accumulated elevated numbers of DSBs as detected by enhanced γ – H2AX foci formation compared to cells with wild-type Rad52 which resulted in a decrease in proliferation and expansion of the Rad52-null LSC population. Expression of wild-type Rad52 in Rad52-null cells decreased the accumulation of DSBs and restored expansion of the LSC population. Inhibition of ROS with the antioxidants Vitamin E or N-acetyl cysteine exerted similar effects on the LSC population of Rad52-null cells as restoration of wild-type Rad52. Our studies also show Rad52's ssDNA-binding activity is required for the proliferation of CML cells as evidenced by the accumulation of DSBs and impairment of clonogenic potential in cells in which the Rad52-F79A ssDNA-binding deficient mutant was expressed. Inhibition of Rad52 DNA binding activity by a peptide aptamer targeting Rad52-F79 resulted in a synthetic lethal phenotype in BCR-ABL1-positive cells due to impairment of the Rad52-dependent HRR pathway, as demonstrated by immunofluorescence and HRR repair assays. Altogether we identify Rad52 as a novel target in the treatment of CML, and other BRCA1- and/or BRCA2-deficient cancers, by showing induction of synthetic lethality in proliferating BCR-ABL1-positive cells in which Rad52 ssDNA-binding activity is inhibited.

Temple University – Theses

Advisors/Committee Members: Skorski, Tomasz, Sheffield, Joel B., Giordano, Antonio, MD, Tuszynski, George P..

Subjects/Keywords: Molecular biology; Oncology; Cellular biology; BCR-ABL1; chronic myeloid leukemia; DNA repair; RAD52; stem cells

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Morales, K. (2012). RAD52 DNA Binding Activity Can Be Targeted to Eliminate CML Stem Cells. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,190030

Chicago Manual of Style (16^th Edition):

Morales, Kimberly. “RAD52 DNA Binding Activity Can Be Targeted to Eliminate CML Stem Cells.” 2012. Doctoral Dissertation, Temple University. Accessed April 14, 2021. http://digital.library.temple.edu/u?/p245801coll10,190030.

MLA Handbook (7^th Edition):

Morales, Kimberly. “RAD52 DNA Binding Activity Can Be Targeted to Eliminate CML Stem Cells.” 2012. Web. 14 Apr 2021.

Vancouver:

Morales K. RAD52 DNA Binding Activity Can Be Targeted to Eliminate CML Stem Cells. [Internet] [Doctoral dissertation]. Temple University; 2012. [cited 2021 Apr 14]. Available from: http://digital.library.temple.edu/u?/p245801coll10,190030.

Council of Science Editors:

Morales K. RAD52 DNA Binding Activity Can Be Targeted to Eliminate CML Stem Cells. [Doctoral Dissertation]. Temple University; 2012. Available from: http://digital.library.temple.edu/u?/p245801coll10,190030

14. Deenik, Wendy. Prevention of Resistance in Chronic Myeloid Leukemia: the role of combination therapy.

Degree: 2010, Erasmus University Medical Center

URL: http://hdl.handle.net/1765/17773

► textabstractChronic myeloid leukemia (CML) is a rare disease with a worldwide incidence of approximately 1-2 cases per 100,000 individuals. Chronic myeloid leukemia occurs slightly more… (more)

Subjects/Keywords: chronic myeloid leukemia; combination therapy

…Dohme B.V. Bristol-Myers Squibb B.V. Prevention of Resistance in Chronic Myeloid Leukemia… …chronic phase chronic myeloid leukemia. A prospective randomized phase III study. (Ann… …intravenous cytarabine: feasibility in newly diagnosed patients with chronic myeloid leukemia. (… …newly diagnosed patients with chronic myeloid leukemia. Result of the Dutch-Belgian HOVON-51… …leukemic and normal stem cell in the bone marrow of patients with chronic myeloid leukemia. (…

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APA (6^th Edition):

Deenik, W. (2010). Prevention of Resistance in Chronic Myeloid Leukemia: the role of combination therapy. (Doctoral Dissertation). Erasmus University Medical Center. Retrieved from http://hdl.handle.net/1765/17773

Chicago Manual of Style (16^th Edition):

Deenik, Wendy. “Prevention of Resistance in Chronic Myeloid Leukemia: the role of combination therapy.” 2010. Doctoral Dissertation, Erasmus University Medical Center. Accessed April 14, 2021. http://hdl.handle.net/1765/17773.

MLA Handbook (7^th Edition):

Deenik, Wendy. “Prevention of Resistance in Chronic Myeloid Leukemia: the role of combination therapy.” 2010. Web. 14 Apr 2021.

Vancouver:

Deenik W. Prevention of Resistance in Chronic Myeloid Leukemia: the role of combination therapy. [Internet] [Doctoral dissertation]. Erasmus University Medical Center; 2010. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/1765/17773.

Council of Science Editors:

Deenik W. Prevention of Resistance in Chronic Myeloid Leukemia: the role of combination therapy. [Doctoral Dissertation]. Erasmus University Medical Center; 2010. Available from: http://hdl.handle.net/1765/17773

University of California – San Francisco

15. Reyes, Gabriel. Genetic Determinants of Disease Persistence and Overt Off-Target Resistance to TKI Therapy in Chronic Myeloid Leukemia.

Degree: Biomedical Sciences, 2014, University of California – San Francisco

URL: http://www.escholarship.org/uc/item/8xv839jk

► Chronic myeloid leukemia (CML), driven by the fusion protein BCR-ABL1, remains highly responsive to treatment with tyrosine kinase inhibitors (TKIs). Although overt resistance and relapse… (more)

▼ Chronic myeloid leukemia (CML), driven by the fusion protein BCR-ABL1, remains highly responsive to treatment with tyrosine kinase inhibitors (TKIs). Although overt resistance and relapse typically occurs through on-target kinase domain mutations, 25-50% of all resistant cases lack such mutations. Second generation BCR-ABL1 inhibitors, such as dasatinib and nilotinib, retain the ability to inhibit a number of kinase domain mutations. Still a number of mutations, notably the T315I gatekeeper mutation, provides continued resistance and only recently with the approval of ponatinib are we able to inhibit all known kinase domain mutations in BCR-ABL1. With ponatinib approval effective inhibitors for all known drug-resistant mutations are available suggesting that poorly understood overt off-target resistance mechanisms should henceforth constitute a greater percentage of overt clinical resistance. Through the use of CML patient samples we sought to define molecular mediators of disease persistence (the occurrence of a hematologic but no cytogenetic response) and overt off-target resistance (a complete loss of cellular response to BCR-ABL1 inhibition), two poorly understood mechanisms of resistance in CML. Chronic phase CML patients exhibiting overexpression of the EVI1 oncogene displayed disease persistence, while the identification of two blast crisis CML patients exhibiting overt off-target resistance were found to contain EVI1 overexpression in conjunction with activated NRAS. Validation of NRAS Q61K, in CML cell lines, exhibited maintenance of cell viability despite TKI treatment and this overt resistance correlated with increased MAPK signaling. Furthermore, expression of MEK-DD, an activated MEK allele, provided a degree of resistance comparable that seen in NRAS Q61K driven off-target resistance. This establishes MAPK signaling as the main culprit downstream of NRAS that mediates the resistant phenotype. This was further substantiated by identifying sensitivity to MEK inhibition both alone and to an even greater extent in combination with BCR-ABL1 inhibitors. In all, we show that EVI1 overexpression can contribute to disease persistence and the presence of activating RAS mutations can lead to overt resistance to BCR-ABL1 tyrosine kinase inhibitors.

Subjects/Keywords: Biology; Medicine; Biochemistry; BCR-ABL; Chronic Myeloid Leukemia; EVI1; RAS; resistance; tyrosine kinase inhibitor

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Reyes, G. (2014). Genetic Determinants of Disease Persistence and Overt Off-Target Resistance to TKI Therapy in Chronic Myeloid Leukemia. (Thesis). University of California – San Francisco. Retrieved from http://www.escholarship.org/uc/item/8xv839jk

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Reyes, Gabriel. “Genetic Determinants of Disease Persistence and Overt Off-Target Resistance to TKI Therapy in Chronic Myeloid Leukemia.” 2014. Thesis, University of California – San Francisco. Accessed April 14, 2021. http://www.escholarship.org/uc/item/8xv839jk.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Reyes, Gabriel. “Genetic Determinants of Disease Persistence and Overt Off-Target Resistance to TKI Therapy in Chronic Myeloid Leukemia.” 2014. Web. 14 Apr 2021.

Vancouver:

Reyes G. Genetic Determinants of Disease Persistence and Overt Off-Target Resistance to TKI Therapy in Chronic Myeloid Leukemia. [Internet] [Thesis]. University of California – San Francisco; 2014. [cited 2021 Apr 14]. Available from: http://www.escholarship.org/uc/item/8xv839jk.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Reyes G. Genetic Determinants of Disease Persistence and Overt Off-Target Resistance to TKI Therapy in Chronic Myeloid Leukemia. [Thesis]. University of California – San Francisco; 2014. Available from: http://www.escholarship.org/uc/item/8xv839jk

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Saskatchewan

16. Abrishami, Mahsa. GENERATION OF SYNTHETIC ANTIBODIES AS POTENTIAL THERAPEUTICS TO BLOCK IL3–MEDIATED INNATE IMATINIB RESISTANCE IN CHRONIC MEYLOID LEUKEMIA.

Degree: 2018, University of Saskatchewan

URL: http://hdl.handle.net/10388/11711

► This thesis was focused on generation of novel antibodies as therapeutics to block innate imatinib resistance in chronic myeloid leukemia (CML). Tyrosine kinase inhibitor (TKI),… (more)

▼ This thesis was focused on generation of novel antibodies as therapeutics to block innate imatinib resistance in chronic myeloid leukemia (CML). Tyrosine kinase inhibitor (TKI), imatinib, is the standard therapy for CML. Although many patients respond to the conventional TKI chemotherapy, the majority relapse upon withdrawal of treatment (Ross et al., 2013) implicating the inability of TKIs in eradication of leukemic stem cells (LSCs). Accumulating evidence demonstrates that bone marrow stromal cell secreting factors, such as Interleukin 3 (IL3) hinder TKI activity and support CML–LSCs to survive the therapy with innate drug resistance. Therefore, the overall objective of this work was to target IL3 receptor as the biomarker of LSCs in CML. We generated anti–IL3Rα and anti–IL3Rβ antibodies against IL3R using solid phase phage display selection. The phage–displayed antibodies were affinity–matured human anti–mIL3Rα and –β antibodies with nanomolar dissociation for the target proteins that bound to IL3 cell surface receptor on multiple CML cell lines. Anti–IL3Rα and anti–IL3Rβ antibodies successfully impaired IL3 downstream signaling, inhibited IL3–mediated CML cell proliferation, and promoted cell apoptosis and targeted LSCs by disruption of colony formation in vitro. Engraftment of cells treated with anti–IL3Rα and anti–IL3Rβ antibodies showed a prolonged survival of C57BL/6 mouse models that received antibody–treated CML cells. Encouraged by anti–leukemic activity of anti–IL3Rα and anti–IL3Rβ antibodies on CML cells, we used our novel antibodies to engineer anti–IL3Rα–IL3Rα and anti–IL3Rβ–IL3Rβ bivalent and anti–IL3Rβ–IL3Rα bispecific antigen binding fragments (Fabs) to enhance targeting of CML cells. SpyCatcher-SpyTag system was used to join IL3Rα / IL3Rβ mono–Fabs by a covalent bond. The bivalent and bispecific Fab formats against IL3Rα, IL3Rβ, or IL3Rα and IL3Rβ elicited nanomolar dissociation for the targets, bound to CML cells, and impaired IL3 signaling in CML cells in vitro. Remarkably, bivalent Fabs and bispecific Fab induced direct cytotoxicity on CML cells in a dose–dependent manner in vitro. In testing the Synergy / additive effect of Fabs and TKIs, adding imatinib to anti–IL3Rβ–IL3Rβ bivalent or anti–IL3Rβ–IL3Rα bispecific (but not anti–IL3Rα mono–Fab or anti–IL3Rα–IL3Rα bivalent Fab) augmented their cytotoxic potential on CML cells in vitro, suggesting the potential key role of targeting IL3Rβ to deplete CML–LSC. This work provided novel anti–IL3Rα and anti–IL3Rβ antibodies, IL3Rα and IL3Rβ bivalent or bispecific Fabs to specifically target malignant CML blast cells and CML–LSCs. Future studies will advance preclinical strategies for targeted therapy and eradication of LSCs in CML patients. Advisors/Committee Members: DeCoteau, John F, Vizeacoumar, Franco, Uppalapati, Maruti, Freywald, Andrew.

Subjects/Keywords: Synthetic antibodies; IL-3; CML; Chronic myeloid leukemia; Imatinib; Innate Drug Resistance; Therapeutics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Abrishami, M. (2018). GENERATION OF SYNTHETIC ANTIBODIES AS POTENTIAL THERAPEUTICS TO BLOCK IL3–MEDIATED INNATE IMATINIB RESISTANCE IN CHRONIC MEYLOID LEUKEMIA. (Thesis). University of Saskatchewan. Retrieved from http://hdl.handle.net/10388/11711

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Abrishami, Mahsa. “GENERATION OF SYNTHETIC ANTIBODIES AS POTENTIAL THERAPEUTICS TO BLOCK IL3–MEDIATED INNATE IMATINIB RESISTANCE IN CHRONIC MEYLOID LEUKEMIA.” 2018. Thesis, University of Saskatchewan. Accessed April 14, 2021. http://hdl.handle.net/10388/11711.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Abrishami, Mahsa. “GENERATION OF SYNTHETIC ANTIBODIES AS POTENTIAL THERAPEUTICS TO BLOCK IL3–MEDIATED INNATE IMATINIB RESISTANCE IN CHRONIC MEYLOID LEUKEMIA.” 2018. Web. 14 Apr 2021.

Vancouver:

Abrishami M. GENERATION OF SYNTHETIC ANTIBODIES AS POTENTIAL THERAPEUTICS TO BLOCK IL3–MEDIATED INNATE IMATINIB RESISTANCE IN CHRONIC MEYLOID LEUKEMIA. [Internet] [Thesis]. University of Saskatchewan; 2018. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/10388/11711.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Abrishami M. GENERATION OF SYNTHETIC ANTIBODIES AS POTENTIAL THERAPEUTICS TO BLOCK IL3–MEDIATED INNATE IMATINIB RESISTANCE IN CHRONIC MEYLOID LEUKEMIA. [Thesis]. University of Saskatchewan; 2018. Available from: http://hdl.handle.net/10388/11711

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

17. Moreira, Roberta Bitencourt. Caracterização de mutações que conferem resistência ao tratamento com imatinibe.

Degree: 2013, Universidade Federal do Espírito Santo; Mestrado em Biotecnologia; Programa de Pós-Graduação em Biotecnologia; UFES; BR

URL: http://repositorio.ufes.br/handle/10/4464

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A Leucemia… (more)

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Made available in DSpace on 2016-08-29T15:34:30Z (GMT). No. of bitstreams: 1 tese_6281_Dissertação_Roberta Bitencourt Moreira_2013.pdf: 2949871 bytes, checksum: 0c46a98a4735b38e93978376b508fac6 (MD5) Previous issue date: 2013-03-06

A Leucemia mielóide crônica (LMC) é caracterizada por uma alteração citogenética conhecida, o cromossomo Philadelphia (Ph),resultado da translocação recíproca t(9;22)(q34;q11).O gene de fusão bcr-abl codifica uma proteína de fusão com atividade tirosina cinase aumentada que desregula vias de transdução de sinais ligadas a proliferação, apoptose e diferenciação celular. A evolução natural da LMC quando não tratada é trifásica, mas atualmente, esta dinâmica foi alterada a partir do desenvolvimento dos inibidores de tirosina cinase (ITC). O imatinibe (Glivec®, Novartis) foi o primeiro ITC aprovado para o tratamento da LMC. A atualização de oito anos do estudo internacional randomizado do interferon e imatinibe (IRIS), ratificou a eficácia e a segurança do uso de imatinibea longo prazo com uma sobrevida global de 85% e uma sobrevida livre de evento de 81%.Entretanto, algumas mutações no domínio cinasedo gene bcr-ablconferem resistência elevada a um ou mais ITC influenciando a escolha da terapia subsequente como no caso de uma mutação T315I, que é altamente resistente ao imatinibe.Apesar de múltiplos fatores contribuírem para a resistência ao imatinibe, a presença de mutação é mais prevalente e tem sido a mais investigada. Diante disso, foram selecionados pacientes de dois hospitais da Região da Grande Vitória que realizam atendimento aos pacientes portadores de LMC pelo Sistema Único de Saúde (SUS) que são encaminhados para o Laboratório de Biologia Molecular do Centro de Transplante de Medula Óssea (CEMO) do Instituto Nacional de Câncer (INCA) para avaliação da resposta molecular aos ITCs, para análise de mutação. Também foi desenvolvido um banco de dados no Microsoft Access® para LMCque permite relacionar informações clínicas e laboratoriais de citogenética e biologia molecular, facilitando o acompanhamento de pacientes com LMC, a compreensão da evolução da doença e o desenvolvimento de pesquisas biotecnológicas.

The chronic myeloid leukemia (CML) is characterized by a cytogenetic alteration known as Philadelphia chromosome (Ph), a result of reciprocal translocation t (9; 22) (q34; q11). The resulting fusion bcr-abl gene encodes a protein with tyrosine kinase constitutive activity that deregulates signal transduction inducing proliferation, apoptosis, and cellular differentiation. The natural evolution of CML is currently changing with the development of tyrosine kinase inhibitors (TKI). Imatinib (Gleevec® , Novartis) was the first TKI approved for the treatment of CML. The eight-year update of the international randomized study of interferon and imatinib (IRIS), confirmed the efficacy and safety of imatinib in the long term with an overall survival of 85% and an event-free survival of 81%. However, some mutations in the kinase domain BCR-ABL confer resistance to one or more TKI,…

Advisors/Committee Members: Renault, Ilana Zalcberg, von Zeidler, Sandra Lucia Ventorin, Cappelletti, Paola Alejandra, Louro, Iuri Drumond.

Subjects/Keywords: Leucemia Mielóide Crônica; Inibidores de tirosina cinase; Mutação; Chronic Myeloid Leukemia; Tyrosine Kinase Inhibitors; Mutation

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Moreira, R. B. (2013). Caracterização de mutações que conferem resistência ao tratamento com imatinibe. (Masters Thesis). Universidade Federal do Espírito Santo; Mestrado em Biotecnologia; Programa de Pós-Graduação em Biotecnologia; UFES; BR. Retrieved from http://repositorio.ufes.br/handle/10/4464

Chicago Manual of Style (16^th Edition):

Moreira, Roberta Bitencourt. “Caracterização de mutações que conferem resistência ao tratamento com imatinibe.” 2013. Masters Thesis, Universidade Federal do Espírito Santo; Mestrado em Biotecnologia; Programa de Pós-Graduação em Biotecnologia; UFES; BR. Accessed April 14, 2021. http://repositorio.ufes.br/handle/10/4464.

MLA Handbook (7^th Edition):

Moreira, Roberta Bitencourt. “Caracterização de mutações que conferem resistência ao tratamento com imatinibe.” 2013. Web. 14 Apr 2021.

Vancouver:

Moreira RB. Caracterização de mutações que conferem resistência ao tratamento com imatinibe. [Internet] [Masters thesis]. Universidade Federal do Espírito Santo; Mestrado em Biotecnologia; Programa de Pós-Graduação em Biotecnologia; UFES; BR; 2013. [cited 2021 Apr 14]. Available from: http://repositorio.ufes.br/handle/10/4464.

Council of Science Editors:

Moreira RB. Caracterização de mutações que conferem resistência ao tratamento com imatinibe. [Masters Thesis]. Universidade Federal do Espírito Santo; Mestrado em Biotecnologia; Programa de Pós-Graduação em Biotecnologia; UFES; BR; 2013. Available from: http://repositorio.ufes.br/handle/10/4464

Universidade Estadual de Campinas

18. Almeida, Maria Helena de, 1973-. Aderência dos pacientes com leucemia mielóide crônica à terapia com inibidores de tirosino quinase.

Degree: Faculdade de Ciências Médicas; Programa de Pós-Graduação em Clínica Médica, 2013, Universidade Estadual de Campinas

URL: ALMEIDA, Maria Helena de. Aderência dos pacientes com leucemia mielóide crônica à terapia com inibidores de tirosino quinase. 2013. 164 p. Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Campinas, SP. Disponível em: <http://www.repositorio.unicamp.br/handle/REPOSIP/308643>. Acesso em: 22 ago. 2018. ; http://repositorio.unicamp.br/jspui/handle/REPOSIP/308643

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Orientador: Cármino Antonio de Souza

Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas

Made available in DSpace on 2018-08-22T09:59:01Z (GMT). No. of… (more)

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Orientador: Cármino Antonio de Souza

Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas

Made available in DSpace on 2018-08-22T09:59:01Z (GMT). No. of bitstreams: 1 Almeida_MariaHelenade_D.pdf: 2031022 bytes, checksum: 4ca81cfeb49f5ad6382582a5201e8b80 (MD5) Previous issue date: 2013

Resumo: A leucemia mieloide crônica e uma doença clonal, caracterizada por uma translocação recíproca entre os cromossomos 9 e 22. A introdução do tratamento com inibidores de tirosino quinase, administrado por via oral, revolucionou e melhorou drasticamente o tratamento destes pacientes, porem a eficácia deste tratamento esta diretamente relacionada ao uso desta medicação a longo prazo. Pacientes e métodos: 137 pacientes com leucemia mieloide crônica, em uso de inibidores de tirosino quinase, tiveram a sua aderência avaliada em três diferentes momentos: seis meses retrospectivo, seis e doze meses prospectivos. Três diferentes métodos indiretos foram utilizados para a avaliação da aderência: o teste de Morisky, o diário de medicação e o índice de posse da medicação. Resultados: não houve diferença significante quando consideramos os três diferentes momentos em que avaliação foi realizada e o método considerado mais efetivo para a avaliação da aderência foi considerado o índice de posse da medicação (p=0.0001). Considerando as informações acima, o método utilizado para a avaliação da aderência foi o índice de posse da medicação avaliado apos, aproximadamente, 12 meses de analise. A mediana de aderência observada neste estudo foi de 96,5%. Os fatores que influenciaram a aderência foram: nível socioeconômico, qualidade de vida, tempo de uso dos inibidores de tirosino quinase e participação em protocolos de pesquisa clinica. Sendo que pacientes com níveis socioeconômicos mais elevados, com melhor qualidade de vida e que estavam inseridos em protocolos clínicos estavam relacionados com melhores índices de aderência (p=0.01, p=0.007 e p=0.02 respectivamente). Enquanto que pacientes com tempo mais prolongado de uso dos inibidores de tirosino quinase estavam relacionados a piores índices de aderência (p=0.03). Para os pacientes em uso de imatinibe por um período de 24 a 48 meses, em primeira linha de tratamento a aderência foi significativamente melhor em pacientes que apresentavam resposta molecular maior quando comparado ao grupo que não havia atingido este beneficio terapêutico (p=0.04). Apenas 24% da população avaliada mantenve-se completamente aderente no período de avaliação. Conclusões: a manutenção de uma aderência adequado em pacientes com leucemia mieloide crônica em uso de inibidores de tirosino quinase esta relacionado com a obtenção de melhores índices de resposta molecular e consequentemente, melhores resultados terapêuticos. A monitorização continua da aderência nestes pacientes e fundamental para que se atinjam os objetivos x xi terapêuticos. Informações sobre os fatores que podem influenciar a aderência, uma equipe multidisciplinar especializada e treinada para assistir este paciente…

Advisors/Committee Members: UNIVERSIDADE ESTADUAL DE CAMPINAS, Souza, Carmino Antonio de, 1951-, Paula, Erich Vinicius de, Aranha, Francisco Jose Penteado, Simões, Belinda Pinto, Mello, Monika Conchon Ribeiro de.

Subjects/Keywords: Adesão à medicação; Leucemia mielóide crônica; Terapêutica; Medication adherence; Chronic myeloid leukemia; Therapeutics

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APA (6^th Edition):

Almeida, Maria Helena de, 1. (2013). Aderência dos pacientes com leucemia mielóide crônica à terapia com inibidores de tirosino quinase. (Doctoral Dissertation). Universidade Estadual de Campinas. Retrieved from ALMEIDA, Maria Helena de. Aderência dos pacientes com leucemia mielóide crônica à terapia com inibidores de tirosino quinase. 2013. 164 p. Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Campinas, SP. Disponível em: <http://www.repositorio.unicamp.br/handle/REPOSIP/308643>. Acesso em: 22 ago. 2018. ; http://repositorio.unicamp.br/jspui/handle/REPOSIP/308643

Chicago Manual of Style (16^th Edition):

Almeida, Maria Helena de, 1973-. “Aderência dos pacientes com leucemia mielóide crônica à terapia com inibidores de tirosino quinase.” 2013. Doctoral Dissertation, Universidade Estadual de Campinas. Accessed April 14, 2021. ALMEIDA, Maria Helena de. Aderência dos pacientes com leucemia mielóide crônica à terapia com inibidores de tirosino quinase. 2013. 164 p. Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Campinas, SP. Disponível em: <http://www.repositorio.unicamp.br/handle/REPOSIP/308643>. Acesso em: 22 ago. 2018. ; http://repositorio.unicamp.br/jspui/handle/REPOSIP/308643.

MLA Handbook (7^th Edition):

Almeida, Maria Helena de, 1973-. “Aderência dos pacientes com leucemia mielóide crônica à terapia com inibidores de tirosino quinase.” 2013. Web. 14 Apr 2021.

Vancouver:

Almeida, Maria Helena de 1. Aderência dos pacientes com leucemia mielóide crônica à terapia com inibidores de tirosino quinase. [Internet] [Doctoral dissertation]. Universidade Estadual de Campinas; 2013. [cited 2021 Apr 14]. Available from: ALMEIDA, Maria Helena de. Aderência dos pacientes com leucemia mielóide crônica à terapia com inibidores de tirosino quinase. 2013. 164 p. Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Campinas, SP. Disponível em: <http://www.repositorio.unicamp.br/handle/REPOSIP/308643>. Acesso em: 22 ago. 2018. ; http://repositorio.unicamp.br/jspui/handle/REPOSIP/308643.

Council of Science Editors:

Almeida, Maria Helena de 1. Aderência dos pacientes com leucemia mielóide crônica à terapia com inibidores de tirosino quinase. [Doctoral Dissertation]. Universidade Estadual de Campinas; 2013. Available from: ALMEIDA, Maria Helena de. Aderência dos pacientes com leucemia mielóide crônica à terapia com inibidores de tirosino quinase. 2013. 164 p. Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Campinas, SP. Disponível em: <http://www.repositorio.unicamp.br/handle/REPOSIP/308643>. Acesso em: 22 ago. 2018. ; http://repositorio.unicamp.br/jspui/handle/REPOSIP/308643

19. Davies, Samuel. Desenvolvimento, caracterização e efeitos biológicos de nanocápsulas poliméricas contendo ácido lipóico e/ou resveratrol.

Degree: 2019, Brazil

URL: http://hdl.handle.net/10183/201595

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O interesse no uso de antioxidantes na prevenção e tratamento de diferentes patologias vem ganhando espaço nos últimos anos, uma vez que a desregulação do… (more)

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O interesse no uso de antioxidantes na prevenção e tratamento de diferentes patologias vem ganhando espaço nos últimos anos, uma vez que a desregulação do estado redox no organismo está associada ao envelhecimento cutâneo e várias doenças, principalmente relacionada à idade. Dois antioxidantes que vêm sendo muito estudados nos últimos anos com finalidade terapêutica são ácido lipoico (LA) e resveratrol (RSV). O LA possui a habilidade direta de sequestrar espécies reativas de oxigênio (ERO) e interagir com outros antioxidantes, já o RSV possui inúmeros efeitos farmacológicos, seja tanto na prevenção de doenças bem como no seu tratamento. A nanotecnologia vem sendo muito utilizada na estabilização de compostos, e como carreador de fármacos ao seu local de ação. Este trabalho teve como objetivo desenvolver uma metodologia de identificação simultânea do RSV e LA em HPLCUV, conanoencapsular o LA e o RSV em uma nanocáspsula de núcleo lipídico e avaliar o potencial antioxidante e a estabilidade frente a radiação UVA da formulação. Objetivou-se ainda avaliar o efeito antiproliferativo do RSV-LNC contra as células K562 de leucemia mielóide crônica (LMC). Foi possível desenvolver um método de identificação e quantificação simultânea do RSV e LA no HPLC-UV. Os antioxidantes foram incorporados em uma nanocápsula de núcleo lipídico. A conanoencapsulação aumentou a atividade antioxidante bem como a estabilidade dos compostos contra a radiação UVA. Ainda, a conanoencapsulação melhorou o controle da liberação e permeação dos antioxidantes, em modelo de pele de cobra. Na avaliação do tratamento com o RSV-LNC de células K562 de LMC sensíveis e resistentes ao imatinibe, o RSV-LNC foi mais eficiente em comparação ao RSV em solução na redução da viabilidade celular. Também, o RSV-LNC em associação com o Imatinibe mostrou ter efeito sinérgico, com potencial para terapia da LMC. Em conclusão, a nanoencapsulação do RSV e do LA melhorou sua atividade antioxidante e estabilidade. Adicionalmente, a nanoencapsulação do RSV demonstrou efeito antiproliferativo em células K562 de LMC, em sinergismo com imatinibe.

The interest in the use of antioxidants in the prevention and treatment of different pathologies has been intensified in the recent years, since deregulation of the redox state in the organism is associated with aging skin and several diseases. Two antioxidants have been studied in recent years with therapeutic purposes are lipoic acid (LA) and resveratrol (RSV). LA has the ability to sequester reactive oxygen species (ROS) and interact with other antioxidants, while RSV has numerous pharmacological effects, in disease prevention or treatment. Nanotechnology has been widely used in stabilizing compounds and drug delivery. This research aimed to develop a methodology for the simultaneous identification of RSV and LA in HPLC-UV, to conanoencapsulate LA and RSV in lipid core nanocapsules, to evaluate the antioxidant potential and stability of the developed formulations under UVA radiation. This study also aimed to evaluate the…

Advisors/Committee Members: Külkamp-Guerreiro, Irene Clemes.

Subjects/Keywords: Resveratrol; Ácido lipóico; Nanocápsulas; Antioxidantes; Leucemia mielóide crônica; Lipoic acid; Nanocapsules; Antioxidants; Chronic myeloid leukemia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Davies, S. (2019). Desenvolvimento, caracterização e efeitos biológicos de nanocápsulas poliméricas contendo ácido lipóico e/ou resveratrol. (Doctoral Dissertation). Brazil. Retrieved from http://hdl.handle.net/10183/201595

Chicago Manual of Style (16^th Edition):

Davies, Samuel. “Desenvolvimento, caracterização e efeitos biológicos de nanocápsulas poliméricas contendo ácido lipóico e/ou resveratrol.” 2019. Doctoral Dissertation, Brazil. Accessed April 14, 2021. http://hdl.handle.net/10183/201595.

MLA Handbook (7^th Edition):

Davies, Samuel. “Desenvolvimento, caracterização e efeitos biológicos de nanocápsulas poliméricas contendo ácido lipóico e/ou resveratrol.” 2019. Web. 14 Apr 2021.

Vancouver:

Davies S. Desenvolvimento, caracterização e efeitos biológicos de nanocápsulas poliméricas contendo ácido lipóico e/ou resveratrol. [Internet] [Doctoral dissertation]. Brazil; 2019. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/10183/201595.

Council of Science Editors:

Davies S. Desenvolvimento, caracterização e efeitos biológicos de nanocápsulas poliméricas contendo ácido lipóico e/ou resveratrol. [Doctoral Dissertation]. Brazil; 2019. Available from: http://hdl.handle.net/10183/201595

Universidade Estadual de Campinas

20. Rego, Monica Fortes Napoleão do, 1960-. Leucemia mieloide crônica : aspectos clínicos e fatores que infuenciaram a resposta citogenética em pacientes tratados com imatinibe no estado do Piauí.

Degree: Faculdade de Ciências Médicas; Programa de Pós-Graduação em Ciências Médicas, 2014, Universidade Estadual de Campinas

URL: REGO, Monica Fortes Napoleão do. Leucemia mieloide crônica: aspectos clínicos e fatores que infuenciaram a resposta citogenética em pacientes tratados com imatinibe no estado do Piauí. 2014. 71 f. Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Campinas, SP. Disponível em: <http://www.repositorio.unicamp.br/handle/REPOSIP/312722>. Acesso em: 25 ago. 2018. ; http://repositorio.unicamp.br/jspui/handle/REPOSIP/312722

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Orientador: Irene Gyongyver Heidemarie Lorand Metze

Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas

Made available in DSpace on 2018-08-26T02:52:00Z (GMT). No.… (more)

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Orientador: Irene Gyongyver Heidemarie Lorand Metze

Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas

Made available in DSpace on 2018-08-26T02:52:00Z (GMT). No. of bitstreams: 1 Rego_MonicaFortesNapoleaodo_D.pdf: 1896028 bytes, checksum: d0c30f6192c810b425474ce94b9f276b (MD5) Previous issue date: 2014

Resumo: A Leucemia Mieloide Crônica (LMC) é uma neoplasia mieloproliferativa, caracterizada pela presença do cromossomo Philadelphia, que é o resultado da translocação balanceada entre os braços longos dos cromossomos 9 e 22 que corresponde à formação do gene híbrido BCR-ABL, que codifica uma proteína quimérica com atividade tirosina-quinase, diretamente implicada na patogênese da doença. O mesilato de imatinibe (IM) é um inibidor seletivo dessa enzima e tem sido usado como terapia alvo-específica na LMC com excelentes resultados em estudos clínicos. É controverso na literatura se estes resultados sao reproduzíveis na população em geral e que processos podem ser implementados para otimizá-los. No nosso estudo realizamos uma análise de pacientes com LMC que tomaram IM entre 2002 e 2013, atendidos no Hospital São Marcos, em Teresina-PI. Teve, como objetivo, caracterizar a LMC no Piauí do ponto de visto clínico e laboratorial, avaliar a eficácia do tratamento com IM em portadores de LMC fase crônica e acelerada, através da resposta citogenética aos 12 meses. Investigou-se a influência dos seguintes fatores na resposta citogenética completa aos 12 meses: idade, sexo, fase da doença, tempo entre o diagnóstico e o início do IM, anos de escolaridade, renda per capita (em reais), distância da moradia ao hospital em Km e escores prognósticos. Cento e quarenta e quatro pacientes foram elegíveis, sendo que 130 deles em fase crônica e 14 em fase acelerada. A mediana de idade foi de 41 anos (8-81). Setenta e seis (52,2%) foram do sexo masculino. Oitenta e cinco (59%) pacientes estavam em fase crônica precoce (menos de um ano entre diagnóstico e início do tratamento). A mediana de escolaridade foi de 4 anos (0-17). Em relação aos índices prognósticos, 89% dos casos foram de risco intermediário ou alto no escore de Sokal, 40% o foram no escore de Hasford, enquanto que a maioria foi de baixo risco no de Eutos. Aos doze meses, 68 casos entraram em resposta citogenética completa. Foram significantes para resposta citogenética aos 12 meses, a escolaridade (p=0, 001), o escore de Hasford (p = 0, 007) e o período entre o diagnóstico e o início do imatinibe (p=0, 001). A mediana de seguimento foi de 65 meses (7-149). Ao término da avaliação 60 (52,8%) pacientes ainda faziam uso do mesilato de imatinibe e 41 (29,4%) tinham descontinuado a medicação (35 por perda de resposta e 6 por progressão). O fato de oito pacientes terem critérios de fase acelerada ao diagnóstico não influiu no resultado do tratamento. Desde que o Ministério da Saúde forneceu o medicamento, o tratamento alvo-específico na LMC produziu excelentes resultados em Teresina. Foi mais importante para o resultado a introdução precoce…

Advisors/Committee Members: UNIVERSIDADE ESTADUAL DE CAMPINAS, Lorand-Metze, Irene, 1945-, Metze, Irene Gyongyver Heidemarie Lorand, 1945-, Campelo, Viriato, Hokama, Paula de Oliveira Montadorn, Vigorio, Afonso Celso, Paula, Erich Vinicius de.

Subjects/Keywords: Leucemia mielóide crônica; Análise citogenética; Prognóstico; Epidemiologia; Chronic myeloid leukemia; Cytogenetic analysis; Prognosis; Epidemiology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Rego, Monica Fortes Napoleão do, 1. (2014). Leucemia mieloide crônica : aspectos clínicos e fatores que infuenciaram a resposta citogenética em pacientes tratados com imatinibe no estado do Piauí. (Doctoral Dissertation). Universidade Estadual de Campinas. Retrieved from REGO, Monica Fortes Napoleão do. Leucemia mieloide crônica: aspectos clínicos e fatores que infuenciaram a resposta citogenética em pacientes tratados com imatinibe no estado do Piauí. 2014. 71 f. Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Campinas, SP. Disponível em: <http://www.repositorio.unicamp.br/handle/REPOSIP/312722>. Acesso em: 25 ago. 2018. ; http://repositorio.unicamp.br/jspui/handle/REPOSIP/312722

Chicago Manual of Style (16^th Edition):

Rego, Monica Fortes Napoleão do, 1960-. “Leucemia mieloide crônica : aspectos clínicos e fatores que infuenciaram a resposta citogenética em pacientes tratados com imatinibe no estado do Piauí.” 2014. Doctoral Dissertation, Universidade Estadual de Campinas. Accessed April 14, 2021. REGO, Monica Fortes Napoleão do. Leucemia mieloide crônica: aspectos clínicos e fatores que infuenciaram a resposta citogenética em pacientes tratados com imatinibe no estado do Piauí. 2014. 71 f. Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Campinas, SP. Disponível em: <http://www.repositorio.unicamp.br/handle/REPOSIP/312722>. Acesso em: 25 ago. 2018. ; http://repositorio.unicamp.br/jspui/handle/REPOSIP/312722.

MLA Handbook (7^th Edition):

Rego, Monica Fortes Napoleão do, 1960-. “Leucemia mieloide crônica : aspectos clínicos e fatores que infuenciaram a resposta citogenética em pacientes tratados com imatinibe no estado do Piauí.” 2014. Web. 14 Apr 2021.

Vancouver:

Rego, Monica Fortes Napoleão do 1. Leucemia mieloide crônica : aspectos clínicos e fatores que infuenciaram a resposta citogenética em pacientes tratados com imatinibe no estado do Piauí. [Internet] [Doctoral dissertation]. Universidade Estadual de Campinas; 2014. [cited 2021 Apr 14]. Available from: REGO, Monica Fortes Napoleão do. Leucemia mieloide crônica: aspectos clínicos e fatores que infuenciaram a resposta citogenética em pacientes tratados com imatinibe no estado do Piauí. 2014. 71 f. Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Campinas, SP. Disponível em: <http://www.repositorio.unicamp.br/handle/REPOSIP/312722>. Acesso em: 25 ago. 2018. ; http://repositorio.unicamp.br/jspui/handle/REPOSIP/312722.

Council of Science Editors:

Rego, Monica Fortes Napoleão do 1. Leucemia mieloide crônica : aspectos clínicos e fatores que infuenciaram a resposta citogenética em pacientes tratados com imatinibe no estado do Piauí. [Doctoral Dissertation]. Universidade Estadual de Campinas; 2014. Available from: REGO, Monica Fortes Napoleão do. Leucemia mieloide crônica: aspectos clínicos e fatores que infuenciaram a resposta citogenética em pacientes tratados com imatinibe no estado do Piauí. 2014. 71 f. Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Campinas, SP. Disponível em: <http://www.repositorio.unicamp.br/handle/REPOSIP/312722>. Acesso em: 25 ago. 2018. ; http://repositorio.unicamp.br/jspui/handle/REPOSIP/312722

21. Hallner, Alexander. Immunotherapy and immunosuppression in myeloid leukemia.

Degree: 2018, University of Gothenburg / Göteborgs Universitet

URL: http://hdl.handle.net/2077/56919

► Acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML) are potentially life-threatening blood cancers characterized by the expansion of malignant myeloid cells in bone marrow… (more)

▼ Acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML) are potentially life-threatening blood cancers characterized by the expansion of malignant myeloid cells in bone marrow and other organs. This thesis aimed at contributing to the understanding of the role of natural killer (NK) cells in AML and CMML with focus on the potential impact of the immunosuppression exerted by reactive oxygen species (ROS) formed by the myeloid cell NOX2 enzyme. The thesis work has comprised in vitro studies of interactions between NK cells and primary myeloid leukemic cells along with analyses of NK cell repertoires in a clinical trial using a NOX2 inhibitor, histamine dihydrochloride (HDC) in conjunction with the NK cell-activating cytokine interleukin-2 (IL-2) for the prevention of relapse of AML after the completion of chemotherapy. Paper I reports that the functions and viability of cytotoxic lymphocytes, including NK cells, were compromised by ROS produced by leukemic myeloid cells recovered from patients with CMML. The results are thus suggestive of a novel mechanism of leukemia-induced immunosuppression in this disease. Paper II analyzed aspects of myeloid cell populations in AML using blood samples from a clinical phase IV trial where AML patients (n=84) received HDC in conjunction with IL-2. The results imply that HDC may exert anti-leukemic efficacy by facilitating the maturation of myeloid cells, which impacts on the efficiency of immunotherapy with HDC/IL-2. In papers III and IV we explored the role of killer cell immunoglobulin-like receptors (KIR) for the relapse and survival of AML patients receiving HDC/IL-2. The results suggest that a subset of immature NK cells with low KIR expression may determine clinical outcome. In paper IV we further analyzed results from the above-referenced phase IV trial and observed that a past cytomegalovirus (CMV) infection predicted high relapse risk and poor survival, presumably by reducing the pool of immature NK cells. The results of paper V suggest that a dimorphism in the leader peptide of HLA-B is relevant to NK cell-mediated killing of AML cells and to the outcome of immunotherapy. In conclusion, this thesis work presents novel aspects of myeloid cell-induced immunosuppression in AML and CMML and identifies NK cell subsets of potential relevance to the benefit of immunotherapy with HDC/IL-2.

Subjects/Keywords: Natural killer cells; acute myeloid leukemia; histamine dihydrochloride; immunotherapy; reactive oxygen species; chronic myelomonocytic leukemia; NK cell education; NKG2A; HLA; KIR

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Hallner, A. (2018). Immunotherapy and immunosuppression in myeloid leukemia. (Thesis). University of Gothenburg / Göteborgs Universitet. Retrieved from http://hdl.handle.net/2077/56919

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Hallner, Alexander. “Immunotherapy and immunosuppression in myeloid leukemia.” 2018. Thesis, University of Gothenburg / Göteborgs Universitet. Accessed April 14, 2021. http://hdl.handle.net/2077/56919.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Hallner, Alexander. “Immunotherapy and immunosuppression in myeloid leukemia.” 2018. Web. 14 Apr 2021.

Vancouver:

Hallner A. Immunotherapy and immunosuppression in myeloid leukemia. [Internet] [Thesis]. University of Gothenburg / Göteborgs Universitet; 2018. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2077/56919.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Hallner A. Immunotherapy and immunosuppression in myeloid leukemia. [Thesis]. University of Gothenburg / Göteborgs Universitet; 2018. Available from: http://hdl.handle.net/2077/56919

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of New South Wales

22. Hughes, Timothy Peter. Clinical and biological significance of minimal residual disease in patients treated for chronic myeloid leukaemia.

Degree: Medicine. Medicine, 1991, University of New South Wales

URL: http://handle.unsw.edu.au/1959.4/67210 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:67935/SOURCE01?view=true

Subjects/Keywords: Myeloid leukemia; Leukemia; Chronic diseases; Thesis Digitisation Program

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Hughes, T. P. (1991). Clinical and biological significance of minimal residual disease in patients treated for chronic myeloid leukaemia. (Masters Thesis). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/67210 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:67935/SOURCE01?view=true

Chicago Manual of Style (16^th Edition):

Hughes, Timothy Peter. “Clinical and biological significance of minimal residual disease in patients treated for chronic myeloid leukaemia.” 1991. Masters Thesis, University of New South Wales. Accessed April 14, 2021. http://handle.unsw.edu.au/1959.4/67210 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:67935/SOURCE01?view=true.

MLA Handbook (7^th Edition):

Hughes, Timothy Peter. “Clinical and biological significance of minimal residual disease in patients treated for chronic myeloid leukaemia.” 1991. Web. 14 Apr 2021.

Vancouver:

Hughes TP. Clinical and biological significance of minimal residual disease in patients treated for chronic myeloid leukaemia. [Internet] [Masters thesis]. University of New South Wales; 1991. [cited 2021 Apr 14]. Available from: http://handle.unsw.edu.au/1959.4/67210 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:67935/SOURCE01?view=true.

Council of Science Editors:

Hughes TP. Clinical and biological significance of minimal residual disease in patients treated for chronic myeloid leukaemia. [Masters Thesis]. University of New South Wales; 1991. Available from: http://handle.unsw.edu.au/1959.4/67210 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:67935/SOURCE01?view=true

University of Helsinki

23. Rebane, Anni. Overcoming Drug-resistance in Chronic Myeloid Leukemia.

Degree: Medicinska fakulteten, 2015, University of Helsinki

URL: http://hdl.handle.net/10138/231375

► Given the success of first-line treatment in chronic myeloid leukemia (CML), the prevalence of the disease is estimated to increase and more patients are expected… (more)

▼ Given the success of first-line treatment in chronic myeloid leukemia (CML), the prevalence of the disease is estimated to increase and more patients are expected to develop resistance to therapy. Thus, even relatively rare point mutations are likely to become more common. In CML, the uncontrollable division of myeloid cells is caused by a reciprocal translocation of chromosomes 9 and 22, resulting in the Philadelphia chromosome. At the meeting point of the two chromosomes, breakpoint cluster region (BCR) and Abelson proto-oncogene 1 (ABL1) fuse together to form the chimeric fusion oncogene BCR-ABL1, the latter of which, the non-receptor tyrosine kinase ABL1, is the driver of the disease. Since the tyrosine kinase inhibitor (TKI) imatinib became available in 2001, the success of first-line therapy has significantly improved the prognosis of CML patients. However, up to 50% of patients with imatinib-refractory disease develop resistance due to point mutations in ABL1, and the most common mutation to emerge is BCR-ABL1 T315I. The broad-range TKI ponatinib is the only approved TKI that inhibits the kinase activity of BCR-ABL1 T315I, but adverse side effects leave patients with this mutation in need of a better, safer, and more effective treatment. The kinase inhibitor axitinib was shown to be selective for BCR-ABL1 T315I, but mutations that emerge as a consequence of axitinib-resistance have yet to be explored. Moreover, patients with the T315I mutation treated with ponatinib have been reported to develop highly drug-resistant mutations in BCR-ABL1 such as T315M and the E255V/T315I compound mutation. The purpose of this study was to identify mutations that enable cells to develop resistance to the kinase inhibitor axitinib and to find new, potential inhibitors for cells expressing the drug-resistant mutations BCR-ABL1 T315I, BCR-ABL1 T315M, and BCR-ABL1 E255V/T315I. To this end, mouse hematopoietic cell lines were constructed prior to determining cell viability in response to inhibitors in combinations and as independent agents. As a novel finding, cells stably expressing T315M were found to exhibit sensitivity to inhibitors of topoisomerase II and mTOR. Moreover, synthetic lethality occurred in these cells in response to the combined treatment of the allosteric inhibitor asciminib and the TKI ponatinib, although not in clinically relevant doses. The highly resistant cells expressing BCR-ABL1 E255V/T315I, like cells expressing T315I and T315M, showed sensitivity to conventional chemotherapy. Notably, however, three SMAC mimetics displayed selectivity to cells expressing BCR-ABL1 E255V/T315I over cells expressing only the single T315I mutation. Considering that CML is expected to become increasingly prevalent, more patients are estimated to develop resistance to therapy. As even relatively rare mutations in BCR-ABL1 become more common, finding an effective treatment for cells expressing these highly resistant mutations takes us one step closer to identifying a safe and effective treatment for CML patients carrying…

Subjects/Keywords: Chronic myeloid leukemia; CML; leukemia; drug-resistance; point mutations; BCR-ABL1; T315I; T315M; E255V/T315I; high-throughput screening; combination testing; Chronic myeloid leukemia; CML; leukemia; drug-resistance; point mutations; BCR-ABL1; T315I; T315M; E255V/T315I; high-throughput screening; combination testing

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Rebane, A. (2015). Overcoming Drug-resistance in Chronic Myeloid Leukemia. (Masters Thesis). University of Helsinki. Retrieved from http://hdl.handle.net/10138/231375

Chicago Manual of Style (16^th Edition):

Rebane, Anni. “Overcoming Drug-resistance in Chronic Myeloid Leukemia.” 2015. Masters Thesis, University of Helsinki. Accessed April 14, 2021. http://hdl.handle.net/10138/231375.

MLA Handbook (7^th Edition):

Rebane, Anni. “Overcoming Drug-resistance in Chronic Myeloid Leukemia.” 2015. Web. 14 Apr 2021.

Vancouver:

Rebane A. Overcoming Drug-resistance in Chronic Myeloid Leukemia. [Internet] [Masters thesis]. University of Helsinki; 2015. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/10138/231375.

Council of Science Editors:

Rebane A. Overcoming Drug-resistance in Chronic Myeloid Leukemia. [Masters Thesis]. University of Helsinki; 2015. Available from: http://hdl.handle.net/10138/231375

24. Isber, Marc. Caractérisation d’aptamères ADN inhibiteurs de l’activité de STAT5B, une protéine impliquée dans les leucémies : Caracterization of DNA aptamers inhibitors of STAT5B activity, a protein involved in leukemia.

Degree: Docteur es, Biotechnologie, 2016, Compiègne

URL: http://www.theses.fr/2016COMP2305

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STAT5A et B sont des facteurs de transcription qui constituent le point de convergence de nombreux signaux extracellulaires. Parmi leurs fonctions biologiques, ils sont connus… (more)

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STAT5A et B sont des facteurs de transcription qui constituent le point de convergence de nombreux signaux extracellulaires. Parmi leurs fonctions biologiques, ils sont connus pour leur rôle dans le développement et la différentiation des cellules hématopoïétiques. Cependant, un taux d’activation et/ou d’expression élevé de ces protéines aboutit à une prolifération incontrôlée des cellules aboutissant ainsi à une leucémogenèse. Ce présent travail vise à caractériser des aptamères ADN (Apta1 et Apta2) sélectionnés préalablement au sein de notre laboratoire contre STAT5B afin de réguler son activité dans le contexte leucémique. Les aptamères ADN sont des oligonucléotides simple brin qui adoptent une structure 3D et interagissent de manière spécifique avec leurs cibles. Contrairement aux anticorps, ils sont peu immunogènes ; ils possèdent alors un potentiel thérapeutique intéressant. La première partie de ce projet se focalise sur l’étude de la capacité d’Apta1 et Apta2 à interagir avec la forme cellulaire et recombinante de STAT5B par pull down et calorimétrie à titrage isotherme. La seconde partie concerne l’évaluation de l’activité d’Apta2 par l’étude de son effet sur la viabilité d’un modèle de leucémie myéloïde chronique et sur sa capacité à perturber la voie de signalisation impliquant STAT5.

STAT5A and B are common transcription factors that constitute a convergent point for many cellular pathways. Among their multiple biological functions, they are well known in promoting immune cell development and differentiation. When some oncogenic mutations occur, STAT5A and B are highly activated leading to uncontrolled proliferation and then to leukemia. Thus, they constitute a prime target to therapeutic intervention. In this work, we characterize new DNA aptamers (Apta1 and Apta2) selected previously by our laboratory against STAT5B. DNA aptamers are single stranded DNA molecules that can adopt 3D structures and recognize specific targets. Unlike antibodies, they fail to induce the immune response: they emerge as potentiel therapeutic molecules. In the first part of this work, the selected aptamers were assessed on their ability to interact with the cellular and recombinant form of STAT5B by using pull down assay and Isothermal Titration Calorimetry. In the second part, we focused on evaluating the effect of Apta2 on chronic myeloid leukemia cell line. For this purpose, cell viability, apoptosis process and JAK-STAT5 signaling pathway were depicted when cells are treated with Apta2.

Advisors/Committee Members: Bihan-Avalle, Bérangère (thesis director).

Subjects/Keywords: Leucémogenèse; STAT5B; Apta1; Apta2; Cellules hématopoïétiques; SELEX (Systematic Evolution of Ligands by EXponential enrichment); DNA; Leukemogenesis; Chronic myeloid leukemia; Hematopoiesis; Leukemia inhibitory factor; Leukemia; Transcription factors; Proteins; Oligonucleotides

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Isber, M. (2016). Caractérisation d’aptamères ADN inhibiteurs de l’activité de STAT5B, une protéine impliquée dans les leucémies : Caracterization of DNA aptamers inhibitors of STAT5B activity, a protein involved in leukemia. (Doctoral Dissertation). Compiègne. Retrieved from http://www.theses.fr/2016COMP2305

Chicago Manual of Style (16^th Edition):

Isber, Marc. “Caractérisation d’aptamères ADN inhibiteurs de l’activité de STAT5B, une protéine impliquée dans les leucémies : Caracterization of DNA aptamers inhibitors of STAT5B activity, a protein involved in leukemia.” 2016. Doctoral Dissertation, Compiègne. Accessed April 14, 2021. http://www.theses.fr/2016COMP2305.

MLA Handbook (7^th Edition):

Isber, Marc. “Caractérisation d’aptamères ADN inhibiteurs de l’activité de STAT5B, une protéine impliquée dans les leucémies : Caracterization of DNA aptamers inhibitors of STAT5B activity, a protein involved in leukemia.” 2016. Web. 14 Apr 2021.

Vancouver:

Isber M. Caractérisation d’aptamères ADN inhibiteurs de l’activité de STAT5B, une protéine impliquée dans les leucémies : Caracterization of DNA aptamers inhibitors of STAT5B activity, a protein involved in leukemia. [Internet] [Doctoral dissertation]. Compiègne; 2016. [cited 2021 Apr 14]. Available from: http://www.theses.fr/2016COMP2305.

Council of Science Editors:

Isber M. Caractérisation d’aptamères ADN inhibiteurs de l’activité de STAT5B, une protéine impliquée dans les leucémies : Caracterization of DNA aptamers inhibitors of STAT5B activity, a protein involved in leukemia. [Doctoral Dissertation]. Compiègne; 2016. Available from: http://www.theses.fr/2016COMP2305

25. Ma, Leyuan. Targeting Drug Resistance in Chronic Myeloid Leukemia: A Dissertation.

Degree: Interdisciplinary Graduate Program, Molecular, Cell, and Cancer Biology Department, 2016, U of Massachusetts : Med

URL: http://escholarship.umassmed.edu/gsbs_diss/870

► Inhibiting BCR-ABL kinase activity with tyrosine kinase inhibitors (TKIs) has been the frontline therapy for CML. Resistance to TKIs frequently occurs, but the mechanisms… (more)

Subjects/Keywords: Leukemia; Myelogenous; Chronic; BCR-ABL Positive; Antineoplastic Agents; Drug Resistance; Neoplasm; Chronic Myeloid Leukemia; Cellular and Molecular Physiology; Hemic and Lymphatic Diseases; Medicinal Chemistry and Pharmaceutics; Neoplasms; Oncology; Pharmacology; Therapeutics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ma, L. (2016). Targeting Drug Resistance in Chronic Myeloid Leukemia: A Dissertation. (Doctoral Dissertation). U of Massachusetts : Med. Retrieved from http://escholarship.umassmed.edu/gsbs_diss/870

Chicago Manual of Style (16^th Edition):

Ma, Leyuan. “Targeting Drug Resistance in Chronic Myeloid Leukemia: A Dissertation.” 2016. Doctoral Dissertation, U of Massachusetts : Med. Accessed April 14, 2021. http://escholarship.umassmed.edu/gsbs_diss/870.

MLA Handbook (7^th Edition):

Ma, Leyuan. “Targeting Drug Resistance in Chronic Myeloid Leukemia: A Dissertation.” 2016. Web. 14 Apr 2021.

Vancouver:

Ma L. Targeting Drug Resistance in Chronic Myeloid Leukemia: A Dissertation. [Internet] [Doctoral dissertation]. U of Massachusetts : Med; 2016. [cited 2021 Apr 14]. Available from: http://escholarship.umassmed.edu/gsbs_diss/870.

Council of Science Editors:

Ma L. Targeting Drug Resistance in Chronic Myeloid Leukemia: A Dissertation. [Doctoral Dissertation]. U of Massachusetts : Med; 2016. Available from: http://escholarship.umassmed.edu/gsbs_diss/870

Freie Universität Berlin

26. Oberender, Christian. Sequenzierung des NUMB-Gens in Patienten mit Chronischer Myeloischer Leukämie.

Degree: 2014, Freie Universität Berlin

URL: http://dx.doi.org/10.17169/refubium-13110

► Ein besseres Verständnis der molekularbiologischen Vorgänge, die zur Transformation der chronischen myeloischen Leukämie (CML) von der relativ indolenten chronischen Phase (CP) zur fatalen Blastenkrise führen,… (more)

▼ Ein besseres Verständnis der molekularbiologischen Vorgänge, die zur Transformation der chronischen myeloischen Leukämie (CML) von der relativ indolenten chronischen Phase (CP) zur fatalen Blastenkrise führen, ist von entscheidender Bedeutung für das klinische Management von CML-Patienten. Unsere Arbeitsgruppe konnte vorher publizierte Daten bestätigen, die eine höhere Expression von Musashi-2 (MSI2) in der Blastenkrise im Vergleich zur CP zeigten. Eine Funktion von MSI2 im Rahmen der Transformation der CML wird diskutiert1-3. Die Mitglieder der Musashi-Genfamilie gelten als Regulatoren von Zellteilung und Zelldifferenzierung unreifer Zellen und agieren, indem sie die Translation bestimmter mRNAs wie der NUMB mRNA inhibieren4,5. Eine Dysregulation von MSI2 führt zu einer Dysfunktion des NUMB-Notch-Signalweges und daraufhin zu einer verstärkten Proliferation hämatopoietischer Stammzellen (HSC), einer eingeschränkten myeloischen Differenzierung und einer schlechteren Prognose2,3. Wir vermuteten, dass Mutationen im NUMB-Gen den NUMB-Notch-Signalweg deregulieren und zur CML-Transformation beitragen können. Diese Vermutung testete ich, indem ich NUMB cDNA von 22 CML-Patienten, davon 10 in CP und 12 in BP, nach der Sanger-Kettenabbruchmethode sequenzierte. Dafür wurde RNA aus dem peripheren Blut von CML-Patienten extrahiert und revers transkribiert zu cDNA. Das gesamte Transkript des NUMB-Genes wurde mittels PCR amplifiziert und daraufhin sequenziert. Unter den 22 CML-Patienten fanden sich keine Abweichungen der NUMB cDNA-Basensequenz im Vergleich zur publizierten Wildtyp-Sequenz, abgesehen von zwei Einzelnukleotid- polymorphismen (SNP) in der 3‘-untranslatierten Region: rs11625196 (C/G) und rs7202 (C/T) 6,7. Ich konnte keine signifikanten Unterschiede im Auftreten der SNP-Genotypen zwischen gesunden Kontrollpersonen und CML-Patienten oder zwischen CP- und Blastenkrise-Patienten beobachten. Allerdings zeigte sich ein signifikanter Einfluss des rs7202-Genotyps auf die Mortalität von Blastenkrise-Patienten. Diese Beobachtung ist jedoch am ehesten auf ungleiche Therapieregime zurückzuführen. Mfold- und SNPfold-Software sagen einen vernachlässigbaren Effekt der beiden SNPs auf die räumliche NUMB-mRNA-Struktur vorher. Zusammengefasst weisen die Beobachtungen dieser Studie daraufhin, dass NUMB-Mutationen nicht als die primäre Ursache der CML-Transformation anzusehen sind. Dennoch wäre es gerechtfertigt, die Erkenntnisse dieser Studie mit einer größeren Anzahl an CML-Patienten oder auch einer sensitiveren Next-Generation- Sequenzierungsmethode zu überprüfen. Advisors/Committee Members: [email protected] (contact), m (gender), N.N. (firstReferee), N.N. (furtherReferee).

Subjects/Keywords: chronic myeloid leukemia; chronic myelogenous leukemia; CML; NUMB; Sequencing; MSI2; Musashi; blast crisis; progression; 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Oberender, C. (2014). Sequenzierung des NUMB-Gens in Patienten mit Chronischer Myeloischer Leukämie. (Thesis). Freie Universität Berlin. Retrieved from http://dx.doi.org/10.17169/refubium-13110

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Oberender, Christian. “Sequenzierung des NUMB-Gens in Patienten mit Chronischer Myeloischer Leukämie.” 2014. Thesis, Freie Universität Berlin. Accessed April 14, 2021. http://dx.doi.org/10.17169/refubium-13110.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Oberender, Christian. “Sequenzierung des NUMB-Gens in Patienten mit Chronischer Myeloischer Leukämie.” 2014. Web. 14 Apr 2021.

Vancouver:

Oberender C. Sequenzierung des NUMB-Gens in Patienten mit Chronischer Myeloischer Leukämie. [Internet] [Thesis]. Freie Universität Berlin; 2014. [cited 2021 Apr 14]. Available from: http://dx.doi.org/10.17169/refubium-13110.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Oberender C. Sequenzierung des NUMB-Gens in Patienten mit Chronischer Myeloischer Leukämie. [Thesis]. Freie Universität Berlin; 2014. Available from: http://dx.doi.org/10.17169/refubium-13110

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

27. Cabanas, Hélène. Rôle de la signalisation calcique dans la leucémie myéloïde chronique : Role of calcium signaling in chronic myeloid leukemia.

Degree: Docteur es, Aspects moléculaires et cellulaires de la biologie, 2016, Poitiers

URL: http://www.theses.fr/2016POIT2302

►

La Leucémie Myéloïde Chronique (LMC) est une maladie clonale caractérisée par la présence du chromosome Philadelphie codant pour Bcr-Abl, une tyrosine kinase constitutivement active responsable… (more)

▼

La Leucémie Myéloïde Chronique (LMC) est une maladie clonale caractérisée par la présence du chromosome Philadelphie codant pour Bcr-Abl, une tyrosine kinase constitutivement active responsable de la leucémogenèse. Bien que très efficaces, les inhibiteurs de tyrosine kinase (ITKs) restent cependant inactifs sur les cellules souches leucémiques. Ce travail de thèse montre que la signalisation calcique, connue pour réguler de nombreux processus dans les cellules saines et cancéreuses, est importante dans la signalisation cellulaire au décours de la LMC. Le rôle des entrées calciques dépendantes des stocks (SOCEs) médiées par STIM1 (STromal Interaction Molecule 1) et les canaux Orai1 et TRPC1 ainsi que des entrées calciques induites par la thrombine a été étudié dans la leucémogenèse. Nous avons observé une diminution de ces entrées dans les cellules exprimant Bcr-Abl pouvant être expliquée par le changement de stœchiométrie Orai1/STIM1. Ceci entraîne la diminution de l'activation de NFAT (Nuclear Factor of Activated T-cells) ainsi que des conséquences sur la prolifération et la migration cellulaire mais pas sur l'apoptose. De plus, les SOCEs sont restaurées dans les cellules cancéreuses après traitement à l'Imatinib, le principal ITK. Nous proposons alors que l'expression de Bcr-Abl joue un rôle sur l'homéostasie calcique en entraînant une dérégulation générale des fonctions cellulaires dans les cellules leucémiques notamment via la voie PKC (Protein Kinase C). Ainsi, ces résultats montrent une dérégulation des entrées calciques dans les cellules exprimant Bcr-Abl, suggérant que la signalisation calcique puisse être une cible thérapeutique en parallèle avec les ITKs.

Chronic Myeloid Leukemia (CML) is a clonal disease characterized by the presence of the Philadelphia chromosome encoding for Bcr-Abl, a constitutively active tyrosine kinase responsible for leukemogenesis. Although Bcr-Abl tyrosine kinase inhibitors (TKIs) have revolutionized the therapy of Ph+ leukemia, the complete eradication of CML is limited by the emergence of resistance in hematopoietic stem cells. This thesis proposes that calcium (Ca2+) signaling pathways, known to govern a large number of functions in normal and cancer cells, may be important in CML cell signaling. Therefore, we studied the role of Store Operated-Calcium entry (SOCE) (i.e. STromal Interaction Molecule 1 (STIM1), Orai1 and TRPC1 channels) and thrombin induced Ca2+ entry in leukemogenesis. We found a decrease in both calcium entries in Bcr-Abl-expressing cells compared to normal cells. The reduced SOCE seems related to a change in stoichiometry of Orai1/STIM1. This leads to a reduction of the Nuclear Factor of Activated T-cells (NFAT) translocation and functional consequences on cell proliferation and migration but not on apoptosis. Moreover, we showed that SOCE is restored in malignant cells after treatment with Imatinib, the main TKI. We proposed that Bcr-Abl expression could impact on Ca2+ homeostasis enhancing a general disorganization of cell functions in leukemia cells…

Advisors/Committee Members: Bourmeyster, Nicolas (thesis director), Déliot, Nadine (thesis director).

Subjects/Keywords: Leucémie myéloïde chronique; Homéostasie calcique; STIM1/Orai1/TRPC1; Leucémogenèse; Chronic myeloid leukemia; Calcium homeostasis; STIM1/Orai1/TRPC1; Leukemogenesis; 571.6

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Cabanas, H. (2016). Rôle de la signalisation calcique dans la leucémie myéloïde chronique : Role of calcium signaling in chronic myeloid leukemia. (Doctoral Dissertation). Poitiers. Retrieved from http://www.theses.fr/2016POIT2302

Chicago Manual of Style (16^th Edition):

Cabanas, Hélène. “Rôle de la signalisation calcique dans la leucémie myéloïde chronique : Role of calcium signaling in chronic myeloid leukemia.” 2016. Doctoral Dissertation, Poitiers. Accessed April 14, 2021. http://www.theses.fr/2016POIT2302.

MLA Handbook (7^th Edition):

Cabanas, Hélène. “Rôle de la signalisation calcique dans la leucémie myéloïde chronique : Role of calcium signaling in chronic myeloid leukemia.” 2016. Web. 14 Apr 2021.

Vancouver:

Cabanas H. Rôle de la signalisation calcique dans la leucémie myéloïde chronique : Role of calcium signaling in chronic myeloid leukemia. [Internet] [Doctoral dissertation]. Poitiers; 2016. [cited 2021 Apr 14]. Available from: http://www.theses.fr/2016POIT2302.

Council of Science Editors:

Cabanas H. Rôle de la signalisation calcique dans la leucémie myéloïde chronique : Role of calcium signaling in chronic myeloid leukemia. [Doctoral Dissertation]. Poitiers; 2016. Available from: http://www.theses.fr/2016POIT2302

Erasmus University Rotterdam

28. Geelen, Inge. Population-based Registry and Response Monitoring in Chronic Myeloid Leukemia.

Degree: Department of Hematology, 2018, Erasmus University Rotterdam

URL: http://hdl.handle.net/1765/111330

► textabstractObservational studies of the efficacy and safety of tyrosine kinase inhibitor (TKI) treatment in patients with chronic myeloid leukemia (CML) who did not participate in… (more)

Subjects/Keywords: Chronic myeloid leukemia (CML); population-based registry; response monitoring

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Geelen, I. (2018). Population-based Registry and Response Monitoring in Chronic Myeloid Leukemia. (Doctoral Dissertation). Erasmus University Rotterdam. Retrieved from http://hdl.handle.net/1765/111330

Chicago Manual of Style (16^th Edition):

Geelen, Inge. “Population-based Registry and Response Monitoring in Chronic Myeloid Leukemia.” 2018. Doctoral Dissertation, Erasmus University Rotterdam. Accessed April 14, 2021. http://hdl.handle.net/1765/111330.

MLA Handbook (7^th Edition):

Geelen, Inge. “Population-based Registry and Response Monitoring in Chronic Myeloid Leukemia.” 2018. Web. 14 Apr 2021.

Vancouver:

Geelen I. Population-based Registry and Response Monitoring in Chronic Myeloid Leukemia. [Internet] [Doctoral dissertation]. Erasmus University Rotterdam; 2018. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/1765/111330.

Council of Science Editors:

Geelen I. Population-based Registry and Response Monitoring in Chronic Myeloid Leukemia. [Doctoral Dissertation]. Erasmus University Rotterdam; 2018. Available from: http://hdl.handle.net/1765/111330

29. M. Barcella. MAPPING BCR-ABL1 FUSION POINTS IN CHRONIC MYELOID LEUKEMIA BY NEXT GENERATION SEQUENCING.

Degree: 2014, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/231153

► Chronic myeloid leukemia (CML) is a myeloproliferative disorder cytogenetically characterized by a reciprocal translocation between the long arms of chromosome 9 and 22 t(9;22) that… (more)

Subjects/Keywords: chronic myeloid leukemia; next generation sequencing; bioinformatics; BCR-ABL1; Philadelphia chromosome; MRD; translocations; Settore MED/04 - Patologia Generale

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Barcella, M. (2014). MAPPING BCR-ABL1 FUSION POINTS IN CHRONIC MYELOID LEUKEMIA BY NEXT GENERATION SEQUENCING. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/231153

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Barcella, M.. “MAPPING BCR-ABL1 FUSION POINTS IN CHRONIC MYELOID LEUKEMIA BY NEXT GENERATION SEQUENCING.” 2014. Thesis, Università degli Studi di Milano. Accessed April 14, 2021. http://hdl.handle.net/2434/231153.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Barcella, M.. “MAPPING BCR-ABL1 FUSION POINTS IN CHRONIC MYELOID LEUKEMIA BY NEXT GENERATION SEQUENCING.” 2014. Web. 14 Apr 2021.

Vancouver:

Barcella M. MAPPING BCR-ABL1 FUSION POINTS IN CHRONIC MYELOID LEUKEMIA BY NEXT GENERATION SEQUENCING. [Internet] [Thesis]. Università degli Studi di Milano; 2014. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2434/231153.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Barcella M. MAPPING BCR-ABL1 FUSION POINTS IN CHRONIC MYELOID LEUKEMIA BY NEXT GENERATION SEQUENCING. [Thesis]. Università degli Studi di Milano; 2014. Available from: http://hdl.handle.net/2434/231153

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

30. Josselin, Marina. Etude des rétrotransposons LINE-1 dans la leucémie myéloïde chronique : LINE-1 retrotransposon in chronic myeloid leukemia.

Degree: Docteur es, Sciences, technologie, santé. Génétique, 2012, Université de Bordeaux Segalen

URL: http://www.theses.fr/2012BOR21985

►

Le gène hybride BCR-ABL1, responsable de la leucémie myéloïde chronique (LMC), code une protéine à activité tyrosine kinase constitutive. Lors d’une étude transcriptomique menée au… (more)

▼

Le gène hybride BCR-ABL1, responsable de la leucémie myéloïde chronique (LMC), code une protéine à activité tyrosine kinase constitutive. Lors d’une étude transcriptomique menée au laboratoire sur des patients résistants secondaires à l’imatinib, les deux gènes codant les protéines des rétrotransposons LINE-1 ont été trouvés sous exprimés d’environ 20 fois lorsque les patients rechutent. Le rôle des transposons n’a jamais été clairement défini, ils assurent certainement une fonction importante puisqu’ils sont conservés au cours de l’évolution et présents chez tous les organismes. Le but de ce travail a été d’étudier l’implication de LINE-1 dans la LMC. La sous-expression de LINE-1 est-elle une conséquence de la présence de BCR-ABL1 ou une cause de son apparition ? Différents groupes ont montré que les rétrotransposons LINE-1 possédent la capacité de réparation des cassures double-brin de l’ADN. Nous avons fait l’hypothèse qu’une diminution de l’expression des gènes codés par les rétrotransposons LINE-1 entraînerait l’instabilité génétique observée dans la LMC. Une étude réalisée chez des patients atteints de LMC et des sujets contrôles a montré une correlation inverse entre l’expression de LINE-1 et celle de l’oncogène BCR-ABL1. Parallèlement, une étude sur des lignées cellulaires leucémiques humaines BCR-ABL positives et négatives a été réalisée. Nous avons recherché le lien qui existe entre l’expression de LINE 1, de BCR-ABL1 et la réparation des cassures double-brin de l’ADN. Nous avons montré d’une part qu’une inhibition de l’expression de BCR-ABL1 induit une augmentation de l’expression des transposons LINE-1 D’autre part, une diminution de l’expression de LINE-1 entraîne une apparition du transcrit BCR-ABL1 dans les cellules BCR-ABL negatives.

BCR-ABL1 fusion gene, responsible of the chronic myeloid leukemia (CML) encodes a constitutively activated tyrosine kinase protein. Expression of both LINE-1 retrotransposon ORFs were found decreased at the time of imatinib resistance in a comparative transcriptional study focused on secondary resistant patients. The role of retrotransposons is unclear. They are conserved through evolution. This project focuses on the involvement of LINE-1 in CML. Is LINE-1 under expression a result of BCR-ABL1 expression or is it at the origin of BCR ABL1? Different groups have shown that LINE-1 retrotransposons were able to repair DNA double strands breaks. We suggest that LINE-1 under expression could be responsible of genetic instability observed in CML. We show in a study on CML patients and healthy subjects that LINE-1 expression is inverse correlated to BCR-ABL1 expression. Moreover, study on BCR-ABL+ and BCR-ABL- human leukemic cell lines was carried on. First, we show that decrease of BCR-ABL1 expression induces increase of LINE-1 expression. Then that decrease of LINE-1 expression generates BCR-ABL1 transcript in BCR-ABL negatives cell lines.

Advisors/Committee Members: Turcq, Béatrice (thesis director).

Subjects/Keywords: Rétrotransposons LINE-1; Leucémie myéloïde chronique; Instabilité génétique; Réparation de l’ADN; LINE-1 retrotransposons, , ,; Chronic myeloid leukemia; Genomic instability; DNA repair

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Josselin, M. (2012). Etude des rétrotransposons LINE-1 dans la leucémie myéloïde chronique : LINE-1 retrotransposon in chronic myeloid leukemia. (Doctoral Dissertation). Université de Bordeaux Segalen. Retrieved from http://www.theses.fr/2012BOR21985

Chicago Manual of Style (16^th Edition):

Josselin, Marina. “Etude des rétrotransposons LINE-1 dans la leucémie myéloïde chronique : LINE-1 retrotransposon in chronic myeloid leukemia.” 2012. Doctoral Dissertation, Université de Bordeaux Segalen. Accessed April 14, 2021. http://www.theses.fr/2012BOR21985.

MLA Handbook (7^th Edition):

Josselin, Marina. “Etude des rétrotransposons LINE-1 dans la leucémie myéloïde chronique : LINE-1 retrotransposon in chronic myeloid leukemia.” 2012. Web. 14 Apr 2021.

Vancouver:

Josselin M. Etude des rétrotransposons LINE-1 dans la leucémie myéloïde chronique : LINE-1 retrotransposon in chronic myeloid leukemia. [Internet] [Doctoral dissertation]. Université de Bordeaux Segalen; 2012. [cited 2021 Apr 14]. Available from: http://www.theses.fr/2012BOR21985.

Council of Science Editors:

Josselin M. Etude des rétrotransposons LINE-1 dans la leucémie myéloïde chronique : LINE-1 retrotransposon in chronic myeloid leukemia. [Doctoral Dissertation]. Université de Bordeaux Segalen; 2012. Available from: http://www.theses.fr/2012BOR21985

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Open Access Theses and Dissertations