NPM1 and acute myeloid leukemia: Three mechanistically orthogonal pairings exemplify this approach: menin + FLT3 inhibition in NPM1/FLT3 co-mutated AML, LSD1 + venetoclax to collapse aberrant enhancer states, and XPO1 + venetoclax in NPM1-mutant AML to extinguish HOX programs while re-priming apoptosis.