Mutations in the NPM1 gene are one of the most frequent driver mutations in AML and commonly indicate a better risk prognosis. NPM1 encodes the nuclear chaperone protein, NPM, that plays a role in protein formation, ribosome biogenesis, DNA replication, and the cell cycle. Mutations in NPM1 are nearly exclusively in exon 12 and often co-occur with epigenetic modifier mutations, like IDH1 and IDH2.