{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Sung PJ"],"funding":["BLRD VA","U.S. Department of Health & Human Services | NIH | National Cancer Institute","NHLBI NIH HHS","U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute","NCI NIH HHS","American Society of Hematology","U.S. Department of Veterans Affairs","Roswell Park Alliance Foundation, Roswell Park Cancer Institute","Leukemia and Lymphoma Society"],"pagination":["291-301"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11141246"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["38(2)"],"pubmed_abstract":["Internal tandem duplication mutations in fms-like tyrosine kinase 3 (FLT3-ITD) are recurrent in acute myeloid leukemia (AML) and increase the risk of relapse. Clinical responses to FLT3 inhibitors (FLT3i) include myeloid differentiation of the FLT3-ITD clone in nearly half of patients through an unknown mechanism. We identified enhancer of zeste homolog 2 (EZH2), a component of polycomb repressive complex 2 (PRC2), as a mediator of this effect using a proteomic-based screen. FLT3i downregulated EZH2 protein expression and PRC2 activity on H3K27me3. FLT3-ITD and loss-of-function mutations in EZH2 are mutually exclusive in human AML. We demonstrated that FLT3i increase myeloid maturation with reduced stem/progenitor cell populations in murine Flt3-ITD AML. Combining EZH1/2 inhibitors with FL"],"journal":["Leukemia"],"pubmed_title":["FLT3 tyrosine kinase inhibition modulates PRC2 and promotes differentiation in acute myeloid leukemia."],"pmcid":["PMC11141246"],"funding_grant_id":["T32 HL007439","RTAF","I01BX004662","K08 CA230190","P30 CA016056","R25 CA181003","P30 CA008748","I01 BX004662","Special Fellow Award","R50 CA211108","R37 CA226433","R21 CA198621"],"pubmed_authors":["Riedel SS","Bernt KM","Wertheim GB","Carroll M","Levine RL","Kulej K","Meyer SE","Garcia BA","Peresie J","Xie HM","Bryant K","Sidoli S","Manning B","Sung PJ","Nemeth MJ","Pham L","Selvam M","Bowman RL"],"additional_accession":[]},"is_claimable":false,"name":"FLT3 tyrosine kinase inhibition modulates PRC2 and promotes differentiation in acute myeloid leukemia.","description":"Internal tandem duplication mutations in fms-like tyrosine kinase 3 (FLT3-ITD) are recurrent in acute myeloid leukemia (AML) and increase the risk of relapse. Clinical responses to FLT3 inhibitors (FLT3i) include myeloid differentiation of the FLT3-ITD clone in nearly half of patients through an unknown mechanism. We identified enhancer of zeste homolog 2 (EZH2), a component of polycomb repressive complex 2 (PRC2), as a mediator of this effect using a proteomic-based screen. FLT3i downregulated EZH2 protein expression and PRC2 activity on H3K27me3. FLT3-ITD and loss-of-function mutations in EZH2 are mutually exclusive in human AML. We demonstrated that FLT3i increase myeloid maturation with reduced stem/progenitor cell populations in murine Flt3-ITD AML. Combining EZH1/2 inhibitors with FL","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Feb","modification":"2026-06-03T00:34:00.731Z","creation":"2025-04-19T20:45:18.224Z"},"accession":"S-EPMC11141246","cross_references":{"pubmed":["38182819"],"doi":["10.1038/s41375-023-02131-4"]}}