Widespread retention of the untranslocated MLL1 allele in MLLr leukemias, together with studies showing that MLL-fusion oncoproteins (e.g., MLL–AF9) require a wild-type copy of MLL1 to drive leukemogenesis [48], fueled the concept that MLL1 activity is a unique vulnerability in these malignancies. The gene discussed is KMT2A; the disease is leukemia.