Among the TFs that we and others identified to be selectively essential and overexpressed in KMT2A-rearranged leukemia, MEF2C, RUNX2, and MEIS1 are well-established direct targets of KMT2A fusion oncoproteins (Krivtsov et al. 2006, 2019; Bernt et al. 2011), prompting us to consider that one of these TFs drives IRF8 overexpression. The gene discussed is RUNX2; the disease is leukemia.