{"id":{"repo_id":"uwo","oai_identifier":"oai:uwo.scholaris.ca:20.500.14721/36449"},"canonical_url":"https://search.dev.ndltd.org/etd/uwo/oai:uwo.scholaris.ca:20.500.14721/36449","repository":{"repo_id":"uwo","name":"Western University","base_url":"https://uwo.scholaris.ca/server/oai/request"},"display":{"title":"Gene Repression and Cell Cycle Regulation by PU.1 in Acute Myeloid Leukemia","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 Sfpi1BN/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 Sfpi1BN/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.","abstract_html":"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 Sfpi1BN/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 Sfpi1BN/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.","abstract_has_math":false,"creators":["Ziliotto, Rachel GH"],"institution":"The University of Western Ontario","degree_name":"M Sc","degree_level":null,"degree_discipline":"Microbiology and Immunology","degree_department":null,"school":null,"contributors":[],"advisors":["Rodeny DeKoter"],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013-08-22","date_published":"2013-08-22","updated_at":"2026-07-27T21:55:54Z","subjects":["PU.1","AML","transcription factor","myeloid cell","cell cycle","E2F1"],"languages":["en_ca"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/20.500.14721/36449","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Rodeny DeKoter"]},{"key":"dc:creator","label":"Author","values":["Ziliotto, Rachel GH"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2025-07-10T21:21:56Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2025-07-10T21:21:56Z"]},{"key":"dc:date.issued","label":"Date","values":["2013-08-22"]},{"key":"dc:publisher","label":"Institution","values":["The University of Western Ontario"]},{"key":"dc:type","label":"Dc Type","values":["thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Microbiology and Immunology"]},{"key":"thesis:degree_name","label":"Degree Name","values":["M Sc"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["PU.1","AML","transcription factor","myeloid cell","cell cycle","E2F1"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en_ca"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/20.500.14721/36449"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The thesis cover page in the PDF document includes references to Western University’s previous institutional repository platform, known as Scholarship@Western, and links to that platform (beginning with ir.lib.uwo.ca). In citing or referring to this thesis, use the DOI or handle from this page instead. Sample citation: Author name, \"Thesis title.\" (Year). Western University Open Repository. https://doi.org/10.71858/123456."]},{"key":"dc:description.abstract","label":"Abstract","values":["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 Sfpi1BN/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 Sfpi1BN/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."]},{"key":"dc:title","label":"Title","values":["Gene Repression and Cell Cycle Regulation by PU.1 in Acute Myeloid Leukemia"]}]}],"canonical_facts":{"dc:contributor.advisor":["Rodeny DeKoter"],"dc:creator":["Ziliotto, Rachel GH"],"dc:date.accessioned":["2025-07-10T21:21:56Z"],"dc:date.available":["2025-07-10T21:21:56Z"],"dc:date.issued":["2013-08-22"],"dc:description":["The thesis cover page in the PDF document includes references to Western University’s previous institutional repository platform, known as Scholarship@Western, and links to that platform (beginning with ir.lib.uwo.ca). In citing or referring to this thesis, use the DOI or handle from this page instead. Sample citation: Author name, \"Thesis title.\" (Year). Western University Open Repository. https://doi.org/10.71858/123456."],"dc:description.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 Sfpi1BN/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 Sfpi1BN/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."],"dc:identifier.uri":["https://hdl.handle.net/20.500.14721/36449"],"dc:language.iso":["en_ca"],"dc:publisher":["The University of Western Ontario"],"dc:subject":["PU.1","AML","transcription factor","myeloid cell","cell cycle","E2F1"],"dc:title":["Gene Repression and Cell Cycle Regulation by PU.1 in Acute Myeloid Leukemia"],"dc:type":["thesis"],"thesis:degree_discipline":["Microbiology and Immunology"],"thesis:degree_name":["M Sc"]},"updated_at":"2026-07-27T21:55:54Z"}