Prognostic impact of DNMT3A mutation in acute myeloid leukemia with mutated NPM1

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 (FLT3(high); >= 0.5) and considered negligible in those with a wild-type (FLT3WT)/low I...

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Detalles Bibliográficos
Autores: Oñate, Guadalupe, Bataller, Alex, Garrido, Ana, Hoyos Colell, Montserrat, Arnan, Montserrat, Vives, Susana, Coll, Rosa, Tormo, Mar, Sampol, Antonia, Escoda, Lourdes, Salamero, Olga, Garcia, Antoni, Bargay, Joan, Aljarilla, Alba, Nomdedeu, Josep F., Esteve Reyner, Jordi, Sierra, Jorge, Pratcorona, Marta
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/183760
Acceso en línea:https://hdl.handle.net/2445/183760
Access Level:acceso abierto
Palabra clave:Leucèmia mieloide
Enzims
Myeloid leukemia
Enzymes
Descripción
Sumario: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 (FLT3(high); >= 0.5) and considered negligible in those with a wild-type (FLT3WT)/low ITD ratio (FLT3low). Because the comutation of DNMT3A (DNMT3A(mut)) has been suggested to negatively influence prognosis in AMLNPM1, we analyzed the impact of DNMT3A(mut) 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, DNMT3A(mut) status did not have a prognostic impact, with comparable overall survival (P = .2). Prognostic stratification established by FLT3-ITD (FLT3WT = FLT3low > FLT3(high)) was independent of DNMT3A(mut) status. Measurable residual disease (MRD) based on NPM1 quantitative polymerase chain reaction was available for 94 patients. DNMT3A(mut) was associated with a higher number of mutated NPM1 transcripts after induction (P = .012) and first consolidation (C1; P < .001). All DNMT3A(mut) 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, DNMT3A(mut) patients exhibited a trend toward greater risk of molecular relapse (P = .054). In conclusion, DNMT3A(mut) did not modify the overall prognosis exerted by FLT3-ITD in AML-NPM1 despite delayed MRD clearance, possibly because of MRD-driven preemptive intervention.

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