These include mutations known to predict poor prognosis, including DNMT3A and the FLT3-ITD.20 Of particular clinical relevance, around 15% of cases of AML harbor both an NPM1c mutation and a FLT3-ITD, and these patients have a relatively poor prognosis.20 Here, we demonstrate sensitivity to I-BET in both primary human AML cells and a mouse model that carry both an NPM1c mutation and an activating mutation of FLT3, suggesting significant clinical utility in this poor-risk subgroup. Here, DNMT3A is linked to acute myeloid leukemia.