Polycomb Repressive Complex 2 Insufficiency Underlies Myeloid Leukemia in Down Syndrome

This study identifies PRC2 (polycomb repressive complex 2) insufficiency as a key driver of myeloid leukemia development in Down syndrome, demonstrating that loss of PRC2 components (Ezh2) combined with cohesion mutations (Stag2) promotes abnormal megakaryocytic differentiation. The research reveals that chromosome 21-encoded miR-125b accelerates leukemic transformation when both Stag2 and Ezh2 are simultaneously lost, establishing critical molecular mechanisms underlying ML-DS pathogenesis.