Several groups have used small molecule inhibitors to demonstrate the feasibility of pharmacological inhibition of DOT1L enzymatic activity in preclinical models of MLL-rearranged leukemia (43–45) and are now under clinical investigation in a phase I study for adults with advanced hematologic malignancies, including acute leukemia with rearrangement of the MLL gene (NCT01684150). This evidence concerns the gene DOT1L and leukemia.