Nucleophosmin mutation in Southeast Asian acute myeloid leukemia: Eight novel variants, FLT3 coexistence and prognostic impact of NPM1/FLT3 mutations

NPM1 mutations were investigated in 400 Southeast Asian leukemia patients and were detectable in 105 cases (26.25%) of acute myeloid leukemia but in no cases of acute lymphoid leukemia or chronic myeloid leukemia. Eight novel and 5 known mutations were identified. All predicted novel proteins shared the last five amino acids VSLRK with the similar gain of nuclear exporting signal motif as known variants. Older age, high white blood cell and platelet counts, normal cytogenetics, and CD34-negativity were associated with NPM1 mutation. FLT3 mutation was more frequent in mutant NPM1 than wild-type cases (56.8% vs. 25.6%) whereas RAS and AML1 mutations were rarely found. Overall survival analysis based on the NPM1/FLT3 mutational status revealed a better outcome for the NPM1-positive/FLT3-negative subgroup. We conclude that: i) NPM1 mutation represents a common genetic hallmark in Southeast Asian acute myeloid leukemia with a normal karyotype; ii) NPM1 mutants coexisted mainly with FLT3 mutants, but not RAS or AML1; iii) FLT3 mutation had a negative prognostic impact on patients with mutant NPM1.