Acute myeloid leukemia with mutated NPM1 mimics acute promyelocytic leukemia presentation

To investigate clinicopathological and molecular features of NPM1-mutated acute myeloid leukemia that presented with infrequent acute promyelocytic leukemia (APL)-like phenotype and clinical presentation.

Cases with both de novo or secondary Acute Myeloid Leukemia (AML) were retrieved. Data from flow cytometry immunophenotyping, cytogenetics, molecular studies, and clinical presentation were analyzed.

Cases presented with abnormal coagulation parameters and low platelets count; four of them showed a DIC index compatible with overt DIC. Two cases showed Auer rods. In all cases, immunophenotypes mimicked APL: blasts expressed CD33, CD13, and cytoplasmic MPO but did not express CD34, HLA-DR, or CD11b. Notably, CD4 expression was observed in all cases. Neither t(15;17) nor PML/RARα gene rearrangement was detected. NPM1 gene mutation was identified in all cases. In four cases, TET2 or IDH2 co-mutations were identified.

Our findings provide additional evidence of association between NPM1-mutated AML with TET2 or IDH2 co-mutations and the APL-like immunophenotype. This AML subset was found to exist in both de novo and secondary AML. High WBC count and blasts with low to moderate side scatter and significant expression of CD4 are observed features that could assist in the differential diagnosis with APL. The occurrence of significant elevated D-dimer levels, or even overt DIC observed at diagnosis in these cases could be relevant for this AML subtype.