While disrupting the binding of LSD1 to CoREST and GFI1, treatment with irreversible LSD1i also attenuated c-Myc levels, but induced expressions of GFI1, PU.1, p21, and CD11b, inhibiting in vitro growth, inducing differentiation/cell lethality, as well as extending survival in immune-depleted mice engrafted with AML or sAML. Here, SPI1 is linked to acute myeloid leukemia.