Recurrent mutations in multiple components of the cohesin complex in myeloid neoplasms

摘要: Cohesin is a multimeric protein complex that involved in the cohesion of sister chromatids, post-replicative DNA repair and transcriptional regulation. Here we report recurrent mutations deletions involving multiple components cohesin complex, including STAG2, RAD21, SMC1A SMC3, different myeloid neoplasms. These were mostly mutually exclusive occurred 12.1% (19/157) acute leukemia, 8.0% (18/224) myelodysplastic syndromes, 10.2% (9/88) chronic myelomonocytic 6.3% (4/64) myelogenous leukemia 1.3% (1/77) classical myeloproliferative Cohesin-mutated leukemic cells showed reduced amounts chromatin-bound components, suggesting substantial loss binding sites on chromatin. The growth cell lines harboring mutation RAD21 (Kasumi-1 cells) or having severely expression STAG2 (MOLM-13 was suppressed by forced wild-type respectively. findings suggest role for compromised functions leukemogenesis.