Prognostic impact of DNMT3A mutation in acute myeloid leukemia with mutated NPM1
| العنوان: | Prognostic impact of DNMT3A mutation in acute myeloid leukemia with mutated NPM1 |
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| المؤلفون: | Oñate, Guadalupe, Bataller, Alex, Garrido, Ana, Hoyos Colell, Montserrat, Arnan, Montserrat, Vives Polo, Susana, Coll, Rosa, Tormo, Mar, Sampol, Antònia, Escoda, Lourdes, Salamero, Olga, Garcia, Antoni, Bargay, Joan, Aljarilla, Alba, Nomdedeu, Josep, Esteve Reyner, Jordi, Sierra, Jorge, Pratcorona, Marta, Universitat Autònoma de Barcelona |
| المساهمون: | 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 |
| المصدر: | Dipòsit Digital de la UB Universidad de Barcelona Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona Scientia |
| بيانات النشر: | American Society of Hematology, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, NPM1, Neoplasm, Residual, Leucèmia mieloide, Genetic Phenomena::Genetic Variation::Mutation [PHENOMENA AND PROCESSES], Leucèmia mieloide aguda - Prognosi, Intensive chemotherapy, medicine.disease_cause, Allelic ratio, Gastroenterology, DNA Methyltransferase 3A, neoplasias::neoplasias por tipo histológico::leucemia::leucemia mieloide::leucemia mieloide aguda [ENFERMEDADES], fluids and secretions, hemic and lymphatic diseases, Internal medicine, Other subheadings::Other subheadings::/genetics [Other subheadings], Humans, Medicine, Mutational status, In patient, Diagnosis::Prognosis [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], diagnóstico::pronóstico [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], fenómenos genéticos::variación genética::mutación [FENÓMENOS Y PROCESOS], Mutation, Otros calificadores::Otros calificadores::/genética [Otros calificadores], business.industry, Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia, Myeloid::Leukemia, Myeloid, Acute [DISEASES], Nuclear Proteins, hemic and immune systems, Hematology, Prognosis, Acute Myeloid Leukemia with Mutated NPM1, Enzymes, body regions, Leukemia, Myeloid, Acute, Anomalies cromosòmiques, Myeloid leukemia, Leucèmia mieloide aguda - Aspectes genètics, embryonic structures, High ratio, Enzims, business, Nucleophosmin |
| الوصف: | 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). |
| وصف الملف: | application/pdf |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cc5eb2056321aef3f1229bd0613ff1b9Test http://hdl.handle.net/2445/183760Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....cc5eb2056321aef3f1229bd0613ff1b9 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |