Inhibition of LSD1 enhanced H3K4 dimethylation, especially at myeloid differentiation-related genes. TCP combined with ATRA significantly suppressed engraftment of primary human AML cells in NOD-SCID mice and showed stronger anti-leukemic activity, targeting leukemia-initiating cells, than either treatment alone. This evidence concerns the gene KDM1A and acute myeloid leukemia.