FLT3-TKD Mutations Associated With NPM1 Mutations Define a Favorable-risk Group in Patients With Acute Myeloid Leukemia

Abstract

BackgroundOutcome of patients with mutation of the FLT3 tyrosine kinase domain (FLT3-TKD) in acute myeloid leukemia (AML) remains controversial. Patients and MethodsHerein, we present a retrospective study of 126 newly diagnosed patients with AML performed in 2 French centers. ResultsFLT3-TKD mutations represented 12.7% of patients, whereas FLT3-internal tandem duplication (ITD) mutation was observed in 20.6% of AML cases and 1.6% of patients harbored both anomalies. At diagnosis, FLT3-TKD and FLT3-ITD were associated with higher peripheral leukocytes count and a higher blast count in bone marrow (P < 10-4). Mutations of the NPM1 gene were frequently associated to FLT3-TKD (68.7%) and FLT3-ITD (61.5%) mutations compared with FLT3 wild type (WT) patients (P < 10-4). Patients with both FLT3-TKD and NPM1 mutations (n = 12; 9.5%) showed a favorable outcome. Interestingly, mutations in NPM1 gene lost their favorable prognostic when not associated with FLT3-TKD both in univariate and multivariate analyses. ConclusionOur data suggest that FLT3-TKD mutations should be routinely determined at the time of diagnosis. In association with NPM1 mutations, patients should follow the therapeutic schedule of favorable-risk patients with AML.