While Flt3/ITD knock-in alone fails to fully transform and recapitulate human leukemia, ablation of Dnmt3a alone is sufficient to predispose HSCs to malignant transformation, resulting in a spectrum of neoplasms with a prolonged time to disease development.[12] We hypothesized that breeding Flt3ITD/+ mice and the conditional Dnmt3a knock-out would result in shortened survival compared to either mutation alone, cooperating to drive AML development in a greater proportion of mice than Dnmt3af/f alone. Here, DNMT3A is linked to neoplasm.