FLT3-TKD mutations associated to NPM1 mutations define a favorable-risk group in patients with acute myeloid leukemia

Publication date: Available online 13 June 2018Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s): Marielle Perry, Sarah Bertoli, Clément Rocher, Sandrine Hayette, Sophie Ducastelle, Fiorenza Barraco, Hélène Labussière-Wallet, Gilles Salles, Christian Recher, Xavier Thomas, Etienne PaubelleAbstractOutcome of patients with mutation of the FLT3 tyrosine kinase domain (FLT3-TKD) in acute myeloid leukemia (AML) remains controversial. Herein we present a retrospective study of 126 newly diagnosed AML patients performed in two French centers. FLT3-TKD mutations represented 12.7% of patients, while 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 to 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. Our 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 AML patients.
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research