Biology of cohesion-deficient myeloid malignancies

Loss-of-function mutations in members of the cohesin complex occur in 15% of all myeloid malignancies. Dr Daniel Sasca (Cambridge Stem Cell Institute, UK) et al. demonstrated that expression of cohesin members changed upon commitment for the erythroid lineage but not the myeloid lineage. This was reflected in different binding patterns of cohesin to active cis-regulatory elements (promoters/enhancers). During differentiation perturbation of cohesin members led to redistribution of the remaining cohesin proteins to promoters/enhancers, resulting in impaired histone acetylation, 3D-DNA interactions and transcription. In erythroid progenitors this resulted in loss of differentiation, whereas in myeloid progenitors proliferation was induced. According to Sasca, these data provide a mechanistic model for (pre)leukemic development of cohesin-impaired hematopoiesis.

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Last Updated on Thursday 02 August 2018.