NPM1 and acute myeloid leukemia: In summary, while in preclinical models NPM1-mutation has widely been identified as a significant transforming event, which contributes to leukemogenesis, but generally insufficient alone to drive full-blown AML, distinct clonal NPM1-mutated preleukemic populations cannot be found in humans, where the occurrence of NPM1 mutation may largely be considered an AML-defining event [5,123].