The mechanism by which Runx1 loss contributes to AML or MDS is not entirely clear, nor is it understood why de novo AML associated with biallelic loss of function RUNX1 mutations confers a considerably worse prognosis than, for example, de novo AML with the (8;21) translocation [6], [8], [9]. Here, RUNX1 is linked to acute myeloid leukemia.