The near universal retention of a pristine copy of MLL1 in these cancers led to the idea that MLLr leukemias depend on wild-type MLL1 to support the activity of oncogenic MLL1-fusion oncoproteins (Thiel et al., 2010)—a function in turn that depends on insertion of a low-affinity WIN motif within MLL1 into the WIN site of WDR5 (Alicea-Velázquez et al., 2016). The gene discussed is KMT2A; the disease is cancer.