Together, these data demonstrate that, in THP1 AML cells, both irreversible and reversible pharmacologic inhibitors of LSD1 displace the LSD1/RCOR1 complex from its physical interaction with GFI1 and that loss of histone deacetylase activity at GFI1 binding sites is, at least in part, responsible for differentiation. Here, GFI1 is linked to acute myeloid leukemia.