The role of mutations in the cohesin complex in acute myeloid leukemia

Int J Hematol. 2017 Jan;105(1):31-36. doi: 10.1007/s12185-016-2119-7. Epub 2016 Oct 28.


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.

Keywords: Acute myeloid leukemia; Cohesin complex; Hematopoietic stem cells.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Chromatin / genetics
  • Chromatin / metabolism
  • Chromosomal Proteins, Non-Histone / genetics*
  • Chromosomal Proteins, Non-Histone / metabolism
  • Cohesins
  • Gene Expression Regulation, Leukemic
  • Hematopoietic Stem Cells / metabolism
  • Hematopoietic Stem Cells / pathology*
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / pathology*
  • Leukopoiesis
  • Mutation*


  • Cell Cycle Proteins
  • Chromatin
  • Chromosomal Proteins, Non-Histone