title: The role of mutations in the cohesin complex in acute myeloid leukemia.
abstract: Mutations in the members of the cohesin complex have recently been identified as early events in acute myeloid leukemia (AML) pathogenesis. Studies conducted by our lab and others have shown that cohesin mutations or knockdown of cohesin subunits impair hematopoietic differentiation and enforce stem cell programs in both human and mouse hematopoiesis. Furthermore, studies in both models demonstrated global changes in chromatin accessibility and structure, in particular increased accessibility at binding sites for hematopoietic stem and progenitor cell (HSPC) transcription factors. These results suggest that mutations in the cohesin complex may contribute to leukemogenesis through modulation of HSPC chromatin accessibility. Future studies will be necessary to determine the detailed mechanisms mediating these phenotypes.
authors: Division of Hematology, Department of Medicine, Cancer Institute, Stanford University School of Medicine, Stanford, USA.|Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Lokey Stem Cell Building, 265 Campus Drive, Stanford, CA, 94305, USA.
authors: Claire
authors: C
authors: Mazumdar
authors: Division of Hematology, Department of Medicine, Cancer Institute, Stanford University School of Medicine, Stanford, USA. rmajeti@stanford.edu.|Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Lokey Stem Cell Building, 265 Campus Drive, Stanford, CA, 94305, USA. rmajeti@stanford.edu.
authors: Ravindra
authors: R
authors: Majeti
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D015973:Gene Expression Regulation, Leukemic; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D019891:Leukopoiesis; D009154:Mutation; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D000097722:Cohesins
keywords: Acute myeloid leukemia; Cohesin complex; Hematopoietic stem cells