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University of Western Ontario

1. Reyes Batista, Carolina. The Role Of Spi-B And Pu.1 Transcription Factors In B Cell Development And In Suppression Of Leukemogenesis.

Degree: 2018, University of Western Ontario

The E26 transformation-specific transcription factors PU.1 and Spi-B are required for B cell maturation within the bone marrow. PU.1 expression is first detected in hematopoietic stem and progenitor cells, whereas Spi-B levels arise as early as the pro-B cell stage. The expression levels of both factors are maintained as B cells progress in development, and the lack of PU.1 and Spi-B at early stages impairs B cell development and can lead to B-cell leukemia. We hypothesized that PU.1 and Spi-B control events associated with the transition from high to low proliferative stages in B cell development and the absence of these factors favor a state of proliferative stress leading to leukemogenesis. To investigate this, we used a mouse model in which Spi1 was conditionally deleted in B cells by Cre recombinase under control of the Mb1 gene, in Spib deficient mice. We found PU.1 and Spi-B were required in B cell development during the transition from large to small pre-B cells. PU.1 functioned as an accessibility factor for immunoglobulin light chain rearrangement, enabling B cell maturation. We demonstrated that lack of Spi-B and PU.1 leads to B cell leukemia associated with driver mutations in the Janus Kinases genes 1 and 3 genes. Our data suggested that reactive oxygen species generation is a possible mechanism by which genetic damage arises consequently leading to B cell leukemia. This thesis contributes to the elucidation of molecular mechanisms by which the complementary transcription factors PU.1 and Spi-B coordinate B cell development and suppress leukemogenesis.

Subjects/Keywords: B cells; B cell development; transcription factors; PU.1; Spi-B; pre-B cell acute lymphoblastic leukemia; immunology; ChIP-sequencing; RNA-sequencing; Whole-Exome sequencing; mutational signatures; immunoglobulin light chain; V(D)J rearrangement; Cancer Biology; Cell and Developmental Biology; Immunity

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

APA (6th Edition):

Reyes Batista, C. (2018). The Role Of Spi-B And Pu.1 Transcription Factors In B Cell Development And In Suppression Of Leukemogenesis. (Thesis). University of Western Ontario. Retrieved from https://ir.lib.uwo.ca/etd/5614

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

Chicago Manual of Style (16th Edition):

Reyes Batista, Carolina. “The Role Of Spi-B And Pu.1 Transcription Factors In B Cell Development And In Suppression Of Leukemogenesis.” 2018. Thesis, University of Western Ontario. Accessed September 23, 2018. https://ir.lib.uwo.ca/etd/5614.

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

MLA Handbook (7th Edition):

Reyes Batista, Carolina. “The Role Of Spi-B And Pu.1 Transcription Factors In B Cell Development And In Suppression Of Leukemogenesis.” 2018. Web. 23 Sep 2018.

Vancouver:

Reyes Batista C. The Role Of Spi-B And Pu.1 Transcription Factors In B Cell Development And In Suppression Of Leukemogenesis. [Internet] [Thesis]. University of Western Ontario; 2018. [cited 2018 Sep 23]. Available from: https://ir.lib.uwo.ca/etd/5614.

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

Council of Science Editors:

Reyes Batista C. The Role Of Spi-B And Pu.1 Transcription Factors In B Cell Development And In Suppression Of Leukemogenesis. [Thesis]. University of Western Ontario; 2018. Available from: https://ir.lib.uwo.ca/etd/5614

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

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