The pronounced sensitivity of the FLT3-ITD/STAT5A signaling axis to DOT1L inhibition raises the possibility that non-MLL-rearranged leukemias with FLT3-ITD mutations, representing 30–40% of acute myeloid leukemias, may also be susceptible to DOT1L inhibition. Here, DOT1L is linked to acute myeloid leukemia.