From the first recognition of treatment-susceptible fusions in the Philadelphia chromosome to the recent implementation of menin inhibitors, the repertoire of ever-more-effective treatments for high-risk ALL continues to grow, comprising an increasing list of effective anti-leukemia agents: JAK-STAT and proteasome blockers that directly impact cancer biology, molecular markers for initiating the delivery of disease-specific chemotherapy, and immune-modulating and -activating agents. The gene discussed is MEN1; the disease is leukemia.