Nucleophosmin mutation in de-novo acute myeloid leukemia

Acute myeloid leukemia (AML) with mutated nucleophosmin gene (NPM1) has distinctive clinical, hematological and molecular features, and is included as a provisional entity in 2008 World Health Organization classification. In this study, we analyzed the frequency and features of AML with mutated NPM1 in Indian patients.

One-hundred consecutive patients of de-novo AML were evaluated for NPM1 mutation and their features were compared with unmutated NPM1 patients.

AML with mutated NPM1 was seen in 21% cases. There was female preponderance with median age of 51 years. Distinguishing Features in mutated group were less bleeding manifestations and bone pains; more lymphadenopathy; higher median total leukocyte and platelet count; less frequency of pancytopenia and more preserved megakaryocytes. Morphologically, cup-shaped nuclei in peripheral blood blasts correlated with NPM1 mutation (p <0.01), but not bone marrow blasts. Among the French-American-British subtypes, NPM1 mutation was seen in M1, M4 and M2 subtypes but not in M0 and M3. Immunophenotypically, there was statistically significant negativity for CD34, strong association with monocytic markers (especially CD11c), CD123 was seen at higher frequency and higher mean fluorescence intensity (MFI) values for CD33 were observed in mutated cases.

Important findings in this study that have not been highlighted in detail in previous studies in NPM1-mutated cases include less bleeding manifestations and bone pains, lower frequency of pancytopenia and more preserved magakaryocytes, higher CD123 expression and higher MFI values for CD33. Presence of blasts with cup-shaped nuclei correlated with NPM1 mutation.