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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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 recurso: artículo
Fecha de publicación:2022
País:España
Institución:Conselleria de Salut i Consum del Govern de les Illes Balears
Repositorio:Docusalut
Idioma:inglés
OAI Identifier:oai:docusalut.com:20.500.13003/19772
Acceso en línea:https://hdl.handle.net/20.500.13003/19772
Access Level:acceso abierto
Palabra clave:Prognosis
Neoplasm, Residual
Mutation
Leukemia, Myeloid, Acute
Humans
Nuclear Proteins
Humanos
Pronóstico
Proteínas Nucleares
Neoplasia Residual
Leucemia Mieloide Aguda
Mutación
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spelling Prognostic impact of DNMT3A mutation in acute myeloid leukemia with mutated NPM1Onate, GuadalupeBataller, AlexGarrido, AnaHoyos, MontserratArnan, MontserratVives, SusanaColl, RosaTormo, MarSampol Mayol, AntoniaEscoda, LourdesSalamero, OlgaGarcia, Antonio J.Bargay Lleonart, JoanAljarilla, AlbaNomdedeu, Josep F.Esteve, JordiSierra, JorgePratcorona, MartaCETLAM GrpPrognosisNeoplasm, ResidualMutationLeukemia, Myeloid, AcuteHumansNuclear ProteinsHumanosPronósticoProteínas NuclearesNeoplasia ResidualLeucemia Mieloide AgudaMutaciónThe 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.Elsevier20222022-02-0820222022-02-08research articlehttp://purl.org/coar/resource_type/c_2df8fbb1info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.13003/19772reponame:Docusalutinstname:Conselleria de Salut i Consum del Govern de les Illes BalearsInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:docusalut.com:20.500.13003/197722026-06-22T12:44:07Z
dc.title.none.fl_str_mv Prognostic impact of DNMT3A mutation in acute myeloid leukemia with mutated NPM1
title Prognostic impact of DNMT3A mutation in acute myeloid leukemia with mutated NPM1
spellingShingle Prognostic impact of DNMT3A mutation in acute myeloid leukemia with mutated NPM1
Onate, Guadalupe
Prognosis
Neoplasm, Residual
Mutation
Leukemia, Myeloid, Acute
Humans
Nuclear Proteins
Humanos
Pronóstico
Proteínas Nucleares
Neoplasia Residual
Leucemia Mieloide Aguda
Mutación
title_short Prognostic impact of DNMT3A mutation in acute myeloid leukemia with mutated NPM1
title_full Prognostic impact of DNMT3A mutation in acute myeloid leukemia with mutated NPM1
title_fullStr Prognostic impact of DNMT3A mutation in acute myeloid leukemia with mutated NPM1
title_full_unstemmed Prognostic impact of DNMT3A mutation in acute myeloid leukemia with mutated NPM1
title_sort Prognostic impact of DNMT3A mutation in acute myeloid leukemia with mutated NPM1
dc.creator.none.fl_str_mv 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
author Onate, Guadalupe
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv Prognosis
Neoplasm, Residual
Mutation
Leukemia, Myeloid, Acute
Humans
Nuclear Proteins
Humanos
Pronóstico
Proteínas Nucleares
Neoplasia Residual
Leucemia Mieloide Aguda
Mutación
topic Prognosis
Neoplasm, Residual
Mutation
Leukemia, Myeloid, Acute
Humans
Nuclear Proteins
Humanos
Pronóstico
Proteínas Nucleares
Neoplasia Residual
Leucemia Mieloide Aguda
Mutación
description 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.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022-02-08
2022
2022-02-08
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.13003/19772
url https://hdl.handle.net/20.500.13003/19772
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Docusalut
instname:Conselleria de Salut i Consum del Govern de les Illes Balears
instname_str Conselleria de Salut i Consum del Govern de les Illes Balears
reponame_str Docusalut
collection Docusalut
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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