We have previously demonstrated that inhibition of BET proteins alters a specific transcriptional program in MLL-rearranged leukemias, with downregulation of genes within this program, such as BCL2 and C-MYC, leading to the induction of apoptosis and cell cycle arrest.6 On the basis of our demonstration of similar cellular phenotypic consequences following I-BET treatment in sensitive AML cell lines, we hypothesized that downregulation of a similar transcriptional program may have mediated these findings. This evidence concerns the gene MYC and leukemia.