Our studies reveal the coincident genome-wide binding of the HMG-box protein HMG20B with LSD1 and GFI1 in myeloid leukemia cells, and the functional relevance of the interaction of the coiled-coil domain of HMG20B with LSD1 in stabilizing the interaction of LSD1 with GFI1. Here, GFI1 is linked to myeloid leukemia.