Chromatin Organization in Myelodysplastic Syndrome.

Disordered chromatin organization has emerged as a new aspect of pathogenesis of myelodysplastic syndromes (MDS). Characterized by lineage dysplasia and high transformation rate to acute myeloid leukemia (AML), the genetic determinant of MDS is thought to be the main driver of the disease progression. Among the recurrently mutated pathways, alterations of chromatin organization, such as cohesin complex, leads to profound impact on hematopoietic stem cell function and lineage commitment. Cohesin complex is a ring like structure comprised of SMC, RAD21 and STAG proteins that involves in 3D genome organization via loop extrusion in the mammalian cells. The partial loss of functional cohesin ring leads to altered chromatin accessibility specific to key hematopoietic transcription factors, which is thought to be the molecular mechanism of cohesin dysfunction. Currently, there is no specific targeting agents towards cohesin mutant MDS/AML. Potential therapeutic strategies have been proposed based on current understanding of the cohesin mutant leukemogenesis. Here, we will review the recent advances in investigation and targeting approaches against cohesin mutant MDS/AML.