Marielle Perry1, Sarah Bertoli2, Clément Rocher1, Sandrine Hayette3, Sophie Ducastelle1, Fiorenza Barraco1, Hélène Labussière-Wallet1, Gilles Salles4, Christian Recher2, Xavier Thomas1, Etienne Paubelle5. 1. Department of Hematology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre-Bénite, France. 2. Department of Hematology, Institut Universitaire du Cancer de Toulouse - Oncopôle, Toulouse, France. 3. Department of Biology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Bénite, France. 4. Department of Hematology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre-Bénite, France; Faculté de Médecine Lyon-Sud Charles Mérieux, Université Claude Bernard Lyon I, Pierre Bénite, France. 5. Department of Hematology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre-Bénite, France; Faculté de Médecine Lyon-Sud Charles Mérieux, Université Claude Bernard Lyon I, Pierre Bénite, France; LBMC, ENS, CNRS UMR5239, Faculté de Médecine Lyon-Sud, Pierre Bénite, France. Electronic address: etienne.paubelle@chu-lyon.fr.
Abstract
BACKGROUND: Outcome of patients with mutation of the FLT3 tyrosine kinase domain (FLT3-TKD) in acute myeloid leukemia (AML) remains controversial. PATIENTS AND METHODS: Herein, we present a retrospective study of 126 newly diagnosed patients with AML performed in 2 French centers. RESULTS: FLT3-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. CONCLUSION: 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 patients with AML.
BACKGROUND: Outcome of patients with mutation of the FLT3 tyrosine kinase domain (FLT3-TKD) in acute myeloid leukemia (AML) remains controversial. PATIENTS AND METHODS: Herein, we present a retrospective study of 126 newly diagnosed patients with AML performed in 2 French centers. RESULTS:FLT3-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. CONCLUSION: 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 patients with AML.
Authors: Maria Teresa Voso; Richard A Larson; Dan Jones; Guido Marcucci; Thomas Prior; Jürgen Krauter; Michael Heuser; Serena Lavorgna; Josep Nomdedeu; Susan M Geyer; Alison Walker; Andrew H Wei; Jorge Sierra; Miguel A Sanz; Joseph M Brandwein; Theo M de Witte; Joop H Jansen; Dietger Niederwieser; Frederick R Appelbaum; Bruno C Medeiros; Martin S Tallman; Richard F Schlenk; Arnold Ganser; Sergio Amadori; Yuan Cheng; YinMiao Chen; Celine Pallaud; Ling Du; Alfonso Piciocchi; Gerhard Ehninger; John Byrd; Christian Thiede; Konstanze Döhner; Richard M Stone; Hartmut Döhner; Clara D Bloomfield; Francesco Lo-Coco Journal: Blood Adv Date: 2020-10-13
Authors: Nikolaus Jahn; Ekaterina Jahn; Maral Saadati; Lars Bullinger; Richard A Larson; Tiziana Ottone; Sergio Amadori; Thomas W Prior; Joseph M Brandwein; Frederick R Appelbaum; Bruno C Medeiros; Martin S Tallman; Gerhard Ehninger; Michael Heuser; Arnold Ganser; Celine Pallaud; Insa Gathmann; Julia Krzykalla; Axel Benner; Clara D Bloomfield; Christian Thiede; Richard M Stone; Hartmut Döhner; Konstanze Döhner Journal: Leukemia Date: 2022-08-03 Impact factor: 12.883