NPM1c AML represents one of the largest subtypes of AML patients and has a variable prognosis, dependent upon the presence of cooperating mutations.20 For example, co-occurrence of NPM1c with internal tandem duplication of the FLT3 gene (FLT3-ITD) and DNMT3A mutations (as occurs in the OCI-AML3 cell line) is common and confers a relatively poor prognosis.20, 21 Therefore, to further assess the efficacy of I-BET against NPM1c AML in cooperation with a number of other mutations, we utilized leukemia cells from an elegant, recently described murine model. The gene discussed is DNMT3A; the disease is acute myeloid leukemia.