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oai:recercat.cat:11351/96112025-10-24T10:18:21Zcom_2072_378070com_2072_378040col_2072_378092

Prognostic impact of DNMT3A mutation in acute myeloid leukemia with mutated NPM1 Garrido, A. Hoyos Colell, Montserrat Arnan, Montserrat Vives Polo, Susana Oñate, Guadalupe Bataller Torralba, Alex Salamero, Olga Institut Català de la Salut [Oñate G, Garrido A, Hoyos M] Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain. [Bataller A] Hospital Clínic, Barcelona, Spain. [Arnan M] Catalan Institute of Oncology (ICO), Hospital Duran i Reynals, Barcelona, Spain. [Vives S] ICO, Hospital Germans Trias i Pujol, Jose Carreras Leukemia Research Institute, Badalona, Spain. [Salamero O] Vall d’Hebron Hospital Universitari, Barcelona, Spain Vall d'Hebron Barcelona Hospital Campus Leucèmia mieloide aguda - Aspectes genètics Anomalies cromosòmiques Leucèmia mieloide aguda - Prognosi DISEASES::Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia, Myeloid::Leukemia, Myeloid, Acute Other subheadings::Other subheadings::Other subheadings::/genetics PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis ENFERMEDADES::neoplasias::neoplasias por tipo histológico::leucemia::leucemia mieloide::leucemia mieloide aguda Otros calificadores::Otros calificadores::Otros calificadores::/genética FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico Prognostic impact; Mutation; Acute myeloid leukemia Impacte pronòstic; Mutació; Leucèmia mieloide aguda Impacto pronóstico; Mutación; Leucemia mieloide aguda The negative prognostic impact of internal tandem duplication of FLT3 (FLT3-ITD) in patients with acute myeloid leukemia with mutated NPM1 (AML-NPM1) is restricted to those with a higher FLT3-ITD allelic ratio (FLT3high; ≥0.5) and considered negligible in those with a wild-type (FLT3WT)/low ITD ratio (FLT3low). Because the comutation of DNMT3A (DNMT3Amut) has been suggested to negatively influence prognosis in AML-NPM1, we analyzed the impact of DNMT3Amut in FLT3-ITD subsets (absent, low, and high ratios). A total of 164 patients diagnosed with AML-NPM1 included in 2 consecutive CETLAM protocols and with DNMT3A and FLT3 status available were studied. Overall, DNMT3Amut status did not have a prognostic impact, with comparable overall survival (P = .2). Prognostic stratification established by FLT3-ITD (FLT3WT = FLT3low > FLT3high) was independent of DNMT3Amut status. Measurable residual disease (MRD) based on NPM1 quantitative polymerase chain reaction was available for 94 patients. DNMT3Amut was associated with a higher number of mutated NPM1 transcripts after induction (P = .012) and first consolidation (C1; P < .001). All DNMT3Amut patients were MRD+ after C1 (P < .001) and exhibited significant MRD persistence after C2 and C3 (MRD+ vs MRD−; P = .027 and P = .001, respectively). Finally, DNMT3Amut patients exhibited a trend toward greater risk of molecular relapse (P = .054). In conclusion, DNMT3Amut did not modify the overall prognosis exerted by FLT3-ITD in AML-NPM1 despite delayed MRD clearance, possibly because of MRD-driven preemptive intervention. This work was supported in part by the Biomedical Research Institute (IIB Sant-Pau) and the José Carreras Leukemia Research Institute as well as grants from the Catalan Government (PERIS SLT002/16/0043 and AGAUR 2017 SGR 139) and the Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Spain (PI17/01246, PI20/01621 and CM20/00061). 2023-05-24T11:33:33Z 2023-05-24T11:33:33Z 2022-02-08 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Oñate G, Bataller A, Garrido A, Hoyos M, Arnan M, Vives S, et al. Prognostic impact of DNMT3A mutation in acute myeloid leukemia with mutated NPM1. Blood Adv. 2022 Feb 8;6(3):882–90. 2473-9537 https://hdl.handle.net/11351/9611 10.1182/bloodadvances.2020004136 34516636 000754263400016 http://hdl.handle.net/11351/9611 eng Blood Advances;6(3) https://doi.org/10.1182/bloodadvances.2020004136 info:eu-repo/grantAgreement/ES/PERIS2016-2020/SLT002%2F16%2F0043 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess application/pdf American Society of Hematology Scientia