Prognostic impact of immunophenotypic classification for newly diagnosed <i>NPM1</i> ‐mutated acute myeloid leukemia

NPM1 mutations are among the most frequent genetic alterations in acute myeloid leukemia (AML) and have been associated with several immunophenotypic features. This study aims to characterize the immunophenotypic profile of this entity at diagnosis using multiparametric flow cytometry and to evaluate the impact of phenotype classifications on prognosis. Immunophenotypic analysis enabled the identification and characterization of various populations previously described in this entity, including immature (CD117⁺ HLA-DR⁺), neutrophil-committed (CD117^{+/heterogeneous} HLA-DR^-), and monocytic (with variable CD117 expression, HLA-DR⁺, and CD64⁺) leukemic cells, which were identified as leukemic expansions, as well as populations presenting immunophenotypic alterations. Cases were distributed in seven immunophenotypic patterns based on R-classification that considers the presence of the three previously described leukemic cell populations but independently of their proportion and relative distribution. Most of the patients included in this study (30, 33%) exhibited an immature and monocytic leukemic cells population (pattern 4), followed by those patients (16, 18%) with a predominant expansion of immature leukemic cells (pattern 1), and those (16, 18%) characterized by a neutrophil-committed leukemic population (pattern 2). Less frequent patterns included (11, 12%) neutrophil-committed and monocytic cells population (pattern 6), (7, 8%) coexistence of the three populations (pattern 7), (6, 7%) immature and neutrophil-committed leukemic cells population (pattern 5), and (5, 5%) predominant expansion of monocytic leukemic cells population (pattern 3). Our analysis indicated that cases with monocytic leukemic cells population predominance exhibit a trend towards a lower cumulative incidence of relapse compared to other leukemic populations, either as the predominant population or across different immunophenotypic patterns. However, differences did not reach statistical significance. These findings help us to contribute with additional information about the biological and immunophenotypic signature of NPM1-AML.