Pharmacogenetic studies in children with acute lymphoblastic leukemia in Argentina

Autores
Aráoz, Hilda Veronica; D'Aloi, Karina; Foncuberta, Maria Eugenia; Sanchez La Rosa, Christian German; Alonso, Cristina Noemi; Chertkoff, Lilien Patricia; Felice, Marisa
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The aim of this study was to evaluate the influence of the most common genetic variants in methylenetetrahydrofolate reductase (MTHFR), thiopurine methyltransferase (TPMT) and glutathione-S-transferases (GSTs) on the outcome of acute lymphoblastic leukemia (ALL) treatment in Argentinean children. Two hundred and eighty-six patients with ALL treated with two Berlin–Frankfurt–Münster (BFM)-based protocols were analyzed. Ten genetic variants were studied. Toxicity was evaluated during the consolidation phase. Children who received 2 g/m2/day of methotrexate and carried at least one 677T allele in MTHFR showed an increased risk of developing severe leukopenia (p = 0.004) and neutropenia (p = 0.003). Intermediate-risk (IR) patients with a heterozygous TPMT genotype had a higher probability of event-free survival than those with a wild-type genotype. Genotyping of MTHFR polymorphisms might be useful to optimize consolidation therapy, reducing the associated severe hematologic toxicity. Further studies are necessary to establish the usefulness of MTHFR and TPMT variants as additional markers to predict outcome in the IR group.
Fil: Aráoz, Hilda Veronica. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina
Fil: D'Aloi, Karina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); Argentina
Fil: Foncuberta, Maria Eugenia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina
Fil: Sanchez La Rosa, Christian German. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina
Fil: Alonso, Cristina Noemi. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina
Fil: Chertkoff, Lilien Patricia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina
Fil: Felice, Marisa. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina
Materia
All
Tpmt
Mthfr
Gsts
Pharmacogenetics
Pediatrics
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/35937
Acceder
id CONICETDig_d6ba62176d433101e10bf84ae7b179ce
oai_identifier_str oai:ri.conicet.gov.ar:11336/35937
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Pharmacogenetic studies in children with acute lymphoblastic leukemia in ArgentinaAráoz, Hilda VeronicaD'Aloi, KarinaFoncuberta, Maria EugeniaSanchez La Rosa, Christian GermanAlonso, Cristina NoemiChertkoff, Lilien PatriciaFelice, MarisaAllTpmtMthfrGstsPharmacogeneticsPediatricshttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3The aim of this study was to evaluate the influence of the most common genetic variants in methylenetetrahydrofolate reductase (MTHFR), thiopurine methyltransferase (TPMT) and glutathione-S-transferases (GSTs) on the outcome of acute lymphoblastic leukemia (ALL) treatment in Argentinean children. Two hundred and eighty-six patients with ALL treated with two Berlin–Frankfurt–Münster (BFM)-based protocols were analyzed. Ten genetic variants were studied. Toxicity was evaluated during the consolidation phase. Children who received 2 g/m2/day of methotrexate and carried at least one 677T allele in MTHFR showed an increased risk of developing severe leukopenia (p = 0.004) and neutropenia (p = 0.003). Intermediate-risk (IR) patients with a heterozygous TPMT genotype had a higher probability of event-free survival than those with a wild-type genotype. Genotyping of MTHFR polymorphisms might be useful to optimize consolidation therapy, reducing the associated severe hematologic toxicity. Further studies are necessary to establish the usefulness of MTHFR and TPMT variants as additional markers to predict outcome in the IR group.Fil: Aráoz, Hilda Veronica. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; ArgentinaFil: D'Aloi, Karina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); ArgentinaFil: Foncuberta, Maria Eugenia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; ArgentinaFil: Sanchez La Rosa, Christian German. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; ArgentinaFil: Alonso, Cristina Noemi. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; ArgentinaFil: Chertkoff, Lilien Patricia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; ArgentinaFil: Felice, Marisa. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; ArgentinaTaylor & Francis Ltd2014-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/35937Aráoz, Hilda Veronica; D'Aloi, Karina; Foncuberta, Maria Eugenia; Sanchez La Rosa, Christian German; Alonso, Cristina Noemi; et al.; Pharmacogenetic studies in children with acute lymphoblastic leukemia in Argentina; Taylor & Francis Ltd; Leukemia and Lymphoma; 56; 5; 8-2014; 1370-13781042-8194CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.tandfonline.com/doi/abs/10.3109/10428194.2014.951844?journalCode=ilal20info:eu-repo/semantics/altIdentifier/doi/10.3109/10428194.2014.951844info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:12:10Zoai:ri.conicet.gov.ar:11336/35937instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:12:11.145CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Pharmacogenetic studies in children with acute lymphoblastic leukemia in Argentina
title Pharmacogenetic studies in children with acute lymphoblastic leukemia in Argentina
spellingShingle Pharmacogenetic studies in children with acute lymphoblastic leukemia in Argentina
Aráoz, Hilda Veronica
All
Tpmt
Mthfr
Gsts
Pharmacogenetics
Pediatrics
title_short Pharmacogenetic studies in children with acute lymphoblastic leukemia in Argentina
title_full Pharmacogenetic studies in children with acute lymphoblastic leukemia in Argentina
title_fullStr Pharmacogenetic studies in children with acute lymphoblastic leukemia in Argentina
title_full_unstemmed Pharmacogenetic studies in children with acute lymphoblastic leukemia in Argentina
title_sort Pharmacogenetic studies in children with acute lymphoblastic leukemia in Argentina
dc.creator.none.fl_str_mv Aráoz, Hilda Veronica
D'Aloi, Karina
Foncuberta, Maria Eugenia
Sanchez La Rosa, Christian German
Alonso, Cristina Noemi
Chertkoff, Lilien Patricia
Felice, Marisa
author Aráoz, Hilda Veronica
author_facet Aráoz, Hilda Veronica
D'Aloi, Karina
Foncuberta, Maria Eugenia
Sanchez La Rosa, Christian German
Alonso, Cristina Noemi
Chertkoff, Lilien Patricia
Felice, Marisa
author_role author
author2 D'Aloi, Karina
Foncuberta, Maria Eugenia
Sanchez La Rosa, Christian German
Alonso, Cristina Noemi
Chertkoff, Lilien Patricia
Felice, Marisa
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv All
Tpmt
Mthfr
Gsts
Pharmacogenetics
Pediatrics
topic All
Tpmt
Mthfr
Gsts
Pharmacogenetics
Pediatrics
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The aim of this study was to evaluate the influence of the most common genetic variants in methylenetetrahydrofolate reductase (MTHFR), thiopurine methyltransferase (TPMT) and glutathione-S-transferases (GSTs) on the outcome of acute lymphoblastic leukemia (ALL) treatment in Argentinean children. Two hundred and eighty-six patients with ALL treated with two Berlin–Frankfurt–Münster (BFM)-based protocols were analyzed. Ten genetic variants were studied. Toxicity was evaluated during the consolidation phase. Children who received 2 g/m2/day of methotrexate and carried at least one 677T allele in MTHFR showed an increased risk of developing severe leukopenia (p = 0.004) and neutropenia (p = 0.003). Intermediate-risk (IR) patients with a heterozygous TPMT genotype had a higher probability of event-free survival than those with a wild-type genotype. Genotyping of MTHFR polymorphisms might be useful to optimize consolidation therapy, reducing the associated severe hematologic toxicity. Further studies are necessary to establish the usefulness of MTHFR and TPMT variants as additional markers to predict outcome in the IR group.
Fil: Aráoz, Hilda Veronica. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina
Fil: D'Aloi, Karina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); Argentina
Fil: Foncuberta, Maria Eugenia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina
Fil: Sanchez La Rosa, Christian German. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina
Fil: Alonso, Cristina Noemi. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina
Fil: Chertkoff, Lilien Patricia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina
Fil: Felice, Marisa. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina
description The aim of this study was to evaluate the influence of the most common genetic variants in methylenetetrahydrofolate reductase (MTHFR), thiopurine methyltransferase (TPMT) and glutathione-S-transferases (GSTs) on the outcome of acute lymphoblastic leukemia (ALL) treatment in Argentinean children. Two hundred and eighty-six patients with ALL treated with two Berlin–Frankfurt–Münster (BFM)-based protocols were analyzed. Ten genetic variants were studied. Toxicity was evaluated during the consolidation phase. Children who received 2 g/m2/day of methotrexate and carried at least one 677T allele in MTHFR showed an increased risk of developing severe leukopenia (p = 0.004) and neutropenia (p = 0.003). Intermediate-risk (IR) patients with a heterozygous TPMT genotype had a higher probability of event-free survival than those with a wild-type genotype. Genotyping of MTHFR polymorphisms might be useful to optimize consolidation therapy, reducing the associated severe hematologic toxicity. Further studies are necessary to establish the usefulness of MTHFR and TPMT variants as additional markers to predict outcome in the IR group.
publishDate 2014
dc.date.none.fl_str_mv 2014-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/35937
Aráoz, Hilda Veronica; D'Aloi, Karina; Foncuberta, Maria Eugenia; Sanchez La Rosa, Christian German; Alonso, Cristina Noemi; et al.; Pharmacogenetic studies in children with acute lymphoblastic leukemia in Argentina; Taylor & Francis Ltd; Leukemia and Lymphoma; 56; 5; 8-2014; 1370-1378
1042-8194
CONICET Digital
CONICET
url http://hdl.handle.net/11336/35937
identifier_str_mv Aráoz, Hilda Veronica; D'Aloi, Karina; Foncuberta, Maria Eugenia; Sanchez La Rosa, Christian German; Alonso, Cristina Noemi; et al.; Pharmacogenetic studies in children with acute lymphoblastic leukemia in Argentina; Taylor & Francis Ltd; Leukemia and Lymphoma; 56; 5; 8-2014; 1370-1378
1042-8194
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.tandfonline.com/doi/abs/10.3109/10428194.2014.951844?journalCode=ilal20
info:eu-repo/semantics/altIdentifier/doi/10.3109/10428194.2014.951844
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Taylor & Francis Ltd
publisher.none.fl_str_mv Taylor & Francis Ltd
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1844614026677452800
score 13.070432

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