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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Detalhes bibliográficos
Autores: Onate, Guadalupe, Bataller, Alex, Garrido, Ana, Hoyos, Montserrat, Arnan, Montserrat, Vives, Susana, Coll, Rosa, Tormo, Mar, Sampol Mayol, Antonia, Escoda, Lourdes, Salamero, Olga, Garcia, Antonio J., Bargay Lleonart, Joan, Aljarilla, Alba, Nomdedeu, Josep F., Esteve, Jordi, Sierra, Jorge, Pratcorona, Marta, CETLAM Grp
Tipo de documento: artigo
Data de publicação:2022
País:España
Recursos:Conselleria de Salut i Consum del Govern de les Illes Balears
Repositório:Docusalut
Idioma:inglês
OAI Identifier:oai:docusalut.com:20.500.13003/19772
Acesso em linha:https://hdl.handle.net/20.500.13003/19772
Access Level:Acceso aberto
Palavra-chave:Prognosis
Neoplasm, Residual
Mutation
Leukemia, Myeloid, Acute
Humans
Nuclear Proteins
Humanos
Pronóstico
Proteínas Nucleares
Neoplasia Residual
Leucemia Mieloide Aguda
Mutación
Descrição
Resumo: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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