Gene Repression and Cell Cycle Regulation by PU.1 in Acute Myeloid Leukemia

Author

Rachel GH Ziliotto, The University of Western OntarioFollow

Degree

Master of Science

Program

Microbiology and Immunology

Supervisor

Dr. Rodeny DeKoter

Abstract

Acute myeloid leukemia (AML) is associated with mutations or chromosomal translocations in genes encoding transcription factors. PU.1 is a transcription factor that is required for the development of nearly all white blood cell types of the immune system, including B cells, granulocytes, and monocytes. Mutation of the gene encoding PU.1, SPI1 in humans and Sfpi1 in mice, is associated with AML. We hypothesized that reduced expression of PU.1 in Sfpi1^BN/BNmyeloid cells will result in the development of AML in transplanted mice due to reduced repression of E2F1, leading to deregulation of the cell cycle. Results indicate that NOD/SCID/γc^-/- mice transplanted with Sfpi1^BN/BN splenocytes become sick with disease resembling AML. Induction of PU.1 expression results in repression of the cell cycle regulator, E2F1, suggesting PU.1 represses E2F1 in order to enable cell cycle exit and differentiation. Understanding the pathways controlled by PU.1 can be used in therapies for the treatment of AML.

Recommended Citation

Ziliotto, Rachel GH, "Gene Repression and Cell Cycle Regulation by PU.1 in Acute Myeloid Leukemia" (2013). Electronic Thesis and Dissertation Repository. 1513.
https://ir.lib.uwo.ca/etd/1513