We show in this study that combination treatments of LSD1 inhibitors with a DOT1L inhibitor SYC-522 exhibited strong synergism against proliferation of MLL-rearranged leukemia cells, presumably because H3K79 hypermethylation is closely associated with imbalanced H3K4 methylation in MLL-rearranged leukemia. The gene discussed is DOT1L; the disease is leukemia.