These preclinical findings demonstrate that simultaneous inhibition of the menin-KMT2A interaction and XPO1 can be a more effective translational strategy for treating <i>KMT2A-</i>r and <i>NPM1</i>-m AML than MI monotherapy to deepen responses and delay/prevent relapses. This evidence concerns the gene MEN1 and acute myeloid leukemia.