The process of leukemogenesis in DS-ML begins with the presence of trisomy 21 that leads to aberrant hematopoiesis caused by dosage-sensitive genes on chromosome 21 implicated in leukemia predisposition such as ERG, ETS2, RUNX1, DYRK1A, RCAN1, CHAF1B, IFNAR1, IFAR2, IFNGR2, IL10RB and miR-125b-2. Here, RUNX1 is linked to leukemia.