Mutations of NPM1 have been reported in approximately 25-35% of cases of acute myeloid leukemia (AML). The mutations of NPM1 are frameshift mutations in the C-terminus of the protein that alter the C-terminal amino acid sequence and are associated with aberrant cytoplasmic localization of the protein. NPM1 mutations in AML are typically associated with a normal karyotype and may co-exist with FLT3 mutations. The presence of NPM1 mutations has been associated with improved complete remission rates, but not necessarily overall survival, in multivariate analysis including assessment of the variety of more recently discovered mutations that may be present in AML. In addition, cytogenetically normal AML with mutated NPM1, without FLT3 ITD or mutated DNMT3A, has been considered to be a favorable genetic risk group according to some studies, although other studies suggest that coexistant mutations in IDH1 or IDH2 may be required for the favorable risk effect of NPM1.