This region is known to be responsible for the hydrophobic interaction between DNMT3A and its regulatory subunit DNMT3L, an interaction that is required for activation of DNMT3A methyltransferase activity and previously shown to be disrupted by mutations in this region.19 Moreover, previously observed nonsynonymous mutations in AML cluster tightly within this region (shown in Figure 2)20, 21, 22. This evidence concerns the gene DNMT3L and acute myeloid leukemia.