A model of HOXA9 transcriptional activity in AML. (Top) HOXA9 heterodimerizes with MEIS/PBX proteins to promote activation of oncogenic signaling. Transcriptional activation may involve coactivators such as MLL3/4, proteins that modify chromatin to activate gene expression. (Bottom) A novel mechanism of HOXA9-mediated gene repression described in this study. HOXA9 interacts with the SAFB to repress differentiation-associated genes in leukemia cells. HOXA9 through SAFB recruits corepressors NuRD and HP1γ, proteins that modify chromatin to repress gene expression. Figure created with BioRender.com.