Cohesin mutations in myeloid malignancies

We review the role of the cohesin complex in healthy and malignant hematopoiesis

Johann-Christoph Jann; Zuzana Tothova


Scholarcy highlights

  • Cohesin is a multisubunit protein complex that forms a ring-like structure around DNA. It is essential for sister chromatid cohesion, chromatin organization, transcriptional regulation, and DNA damage repair and plays a major role in dynamically shaping the genome architecture and maintaining DNA integrity
  • The core complex subunits STAG2, RAD21, SMC1, and SMC3, as well as its modulators PDS5A/B, WAPL, and NIPBL, have been found to be recurrently mutated in hematologic and solid malignancies. These mutations are found across the full spectrum of myeloid neoplasia, including pediatric Down syndrome‚Äďassociated acute megakaryoblastic leukemia, myelodysplastic syndromes, chronic myelomonocytic leukemia, and de novo and secondary acute myeloid leukemias
  • The mechanisms by which cohesin mutations act as drivers of clonal expansion and disease progression are still poorly understood
  • Recent studies have described the impact of cohesin alterations on self-renewal and differentiation of hematopoietic stem and progenitor cells, which are associated with changes in chromatin and epigenetic state directing lineage commitment, as well as genomic integrity
  • We review the role of the cohesin complex in healthy and malignant hematopoiesis
  • We discuss clinical implications of cohesin mutations in myeloid malignancies and discuss opportunities for therapeutic targeting

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