Potential strategy for targeting leukemic cells harboring NPM1 mutations. NPM1 is one of the most abundant nucleolar protein. NPM1-mutated AML cells are depleted of normal NPM1 (red blocks) in the nucleolus because of both haploinsufficiency and cytoplasmic dislocation (through formation of heterodimers with NPM1 mutant; NPM1m, green blocks). This may explain why they are more sensitive than cells with germ line NPM1 (containing full dose of wild-type NPM1) to drugs that, affecting NPM1 levels or oligomerization lead to disruption of the nucleolar structure and apoptosis.