DNMT3A and acute myeloid leukemia: FLT3/ITD mutations have been shown to be a later event in leukemic clonal revolution.[33, 34] In contrast, loss of DNMT3a is one of the pre-leukemic events found in AML patients.[17, 34] In mouse, DNMT3A is highly expressed in HSCs enabling efficient differentiation through the epigenetic silencing of HSC regulatory genes.[13] Loss of DNMT3a promotes HSC self-renewal at the expense of differentiation.