TP53 codon 72 polymorphism predicts chronic myeloid leukemia susceptibility and treatment outcome

Autores
Weich, Natalia; Ferri, Cristian Alberto; Moiraghi, Elena Beatriz; Bengió, Raquel; Giere, Isabel; Pavlovsky, Carolina; Larripa, Irene Beatriz; Fundia, Ariela Freya
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
BCR-ABL1 gene is a key molecular marker of chronic myeloid leukemia (CML), but it is still unclear which molecular factors may influence CML risk or lead to variable responses to tyrosine kinase inhibitors (TKIs). The aim of this study was to investigate the impact of TP53 c.213 G > C(Arg72Pro; rs1042522) polymorphism on CML risk and its correlation with clinical outcome. Peripheral blood samples from 141 treated CML patients and 141 sex- and age-matched healthy individuals were genotyped by PCR-RFLP. Standard genetic models for disease penetrance were evaluated by logistic regression analysis and Kaplan-Meier method was performed to estimate survival curves. Our study suggests that TP53 c.213 G > C polymorphism may be involved in CML development considering a recessive model (p = 0.01; OR: 0.19; CI: 0.06–0.68). In addition, a non-homogenous distribution was found for this polymorphism in males and patients youngers than 50 years (p = 0.02). According to clinical response, TP53-GG genotype was associated with higher levels of BCR-ABL1 transcripts (p = 0.04) and shorter event free survival (p = 0.04). Moreover, a trend toward significance was found for failure free survival (p = 0.06) and time to imatinib failure (p = 0.08). In conclusion, our data suggest that a; TP53 c.213 G > C may be a potential biomarker of CML susceptibility and clinical outcome.
Fil: Weich, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Ferri, Cristian Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Moiraghi, Elena Beatriz. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina
Fil: Bengió, Raquel. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Giere, Isabel. Fundaleu; Argentina
Fil: Pavlovsky, Carolina. Fundaleu; Argentina
Fil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Fundia, Ariela Freya. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Materia
Leucemia Mieloide Crónica
Polimorfismos en Tp53
Susceptibilidad
Respuesta Terapeutica
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/39511
Acceder
id CONICETDig_33202f57b517803eda9b400cc2afd20f
oai_identifier_str oai:ri.conicet.gov.ar:11336/39511
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling TP53 codon 72 polymorphism predicts chronic myeloid leukemia susceptibility and treatment outcomeWeich, NataliaFerri, Cristian AlbertoMoiraghi, Elena BeatrizBengió, RaquelGiere, IsabelPavlovsky, CarolinaLarripa, Irene BeatrizFundia, Ariela FreyaLeucemia Mieloide CrónicaPolimorfismos en Tp53SusceptibilidadRespuesta Terapeuticahttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3BCR-ABL1 gene is a key molecular marker of chronic myeloid leukemia (CML), but it is still unclear which molecular factors may influence CML risk or lead to variable responses to tyrosine kinase inhibitors (TKIs). The aim of this study was to investigate the impact of TP53 c.213 G > C(Arg72Pro; rs1042522) polymorphism on CML risk and its correlation with clinical outcome. Peripheral blood samples from 141 treated CML patients and 141 sex- and age-matched healthy individuals were genotyped by PCR-RFLP. Standard genetic models for disease penetrance were evaluated by logistic regression analysis and Kaplan-Meier method was performed to estimate survival curves. Our study suggests that TP53 c.213 G > C polymorphism may be involved in CML development considering a recessive model (p = 0.01; OR: 0.19; CI: 0.06–0.68). In addition, a non-homogenous distribution was found for this polymorphism in males and patients youngers than 50 years (p = 0.02). According to clinical response, TP53-GG genotype was associated with higher levels of BCR-ABL1 transcripts (p = 0.04) and shorter event free survival (p = 0.04). Moreover, a trend toward significance was found for failure free survival (p = 0.06) and time to imatinib failure (p = 0.08). In conclusion, our data suggest that a; TP53 c.213 G > C may be a potential biomarker of CML susceptibility and clinical outcome.Fil: Weich, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Ferri, Cristian Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Moiraghi, Elena Beatriz. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Bengió, Raquel. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Giere, Isabel. Fundaleu; ArgentinaFil: Pavlovsky, Carolina. Fundaleu; ArgentinaFil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Fundia, Ariela Freya. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaAcademic Press Inc Elsevier Science2016-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/39511Weich, Natalia; Ferri, Cristian Alberto; Moiraghi, Elena Beatriz; Bengió, Raquel; Giere, Isabel; et al.; TP53 codon 72 polymorphism predicts chronic myeloid leukemia susceptibility and treatment outcome; Academic Press Inc Elsevier Science; Blood Cells Molecules And Diseases; 59; 5-2016; 129-1331079-97961096-0961CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.bcmd.2016.05.007info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1079979616300559info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:46:20Zoai:ri.conicet.gov.ar:11336/39511instacron: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:34982025-09-03 09:46:20.247CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv TP53 codon 72 polymorphism predicts chronic myeloid leukemia susceptibility and treatment outcome
title TP53 codon 72 polymorphism predicts chronic myeloid leukemia susceptibility and treatment outcome
spellingShingle TP53 codon 72 polymorphism predicts chronic myeloid leukemia susceptibility and treatment outcome
Weich, Natalia
Leucemia Mieloide Crónica
Polimorfismos en Tp53
Susceptibilidad
Respuesta Terapeutica
title_short TP53 codon 72 polymorphism predicts chronic myeloid leukemia susceptibility and treatment outcome
title_full TP53 codon 72 polymorphism predicts chronic myeloid leukemia susceptibility and treatment outcome
title_fullStr TP53 codon 72 polymorphism predicts chronic myeloid leukemia susceptibility and treatment outcome
title_full_unstemmed TP53 codon 72 polymorphism predicts chronic myeloid leukemia susceptibility and treatment outcome
title_sort TP53 codon 72 polymorphism predicts chronic myeloid leukemia susceptibility and treatment outcome
dc.creator.none.fl_str_mv Weich, Natalia
Ferri, Cristian Alberto
Moiraghi, Elena Beatriz
Bengió, Raquel
Giere, Isabel
Pavlovsky, Carolina
Larripa, Irene Beatriz
Fundia, Ariela Freya
author Weich, Natalia
author_facet Weich, Natalia
Ferri, Cristian Alberto
Moiraghi, Elena Beatriz
Bengió, Raquel
Giere, Isabel
Pavlovsky, Carolina
Larripa, Irene Beatriz
Fundia, Ariela Freya
author_role author
author2 Ferri, Cristian Alberto
Moiraghi, Elena Beatriz
Bengió, Raquel
Giere, Isabel
Pavlovsky, Carolina
Larripa, Irene Beatriz
Fundia, Ariela Freya
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Leucemia Mieloide Crónica
Polimorfismos en Tp53
Susceptibilidad
Respuesta Terapeutica
topic Leucemia Mieloide Crónica
Polimorfismos en Tp53
Susceptibilidad
Respuesta Terapeutica
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv BCR-ABL1 gene is a key molecular marker of chronic myeloid leukemia (CML), but it is still unclear which molecular factors may influence CML risk or lead to variable responses to tyrosine kinase inhibitors (TKIs). The aim of this study was to investigate the impact of TP53 c.213 G > C(Arg72Pro; rs1042522) polymorphism on CML risk and its correlation with clinical outcome. Peripheral blood samples from 141 treated CML patients and 141 sex- and age-matched healthy individuals were genotyped by PCR-RFLP. Standard genetic models for disease penetrance were evaluated by logistic regression analysis and Kaplan-Meier method was performed to estimate survival curves. Our study suggests that TP53 c.213 G > C polymorphism may be involved in CML development considering a recessive model (p = 0.01; OR: 0.19; CI: 0.06–0.68). In addition, a non-homogenous distribution was found for this polymorphism in males and patients youngers than 50 years (p = 0.02). According to clinical response, TP53-GG genotype was associated with higher levels of BCR-ABL1 transcripts (p = 0.04) and shorter event free survival (p = 0.04). Moreover, a trend toward significance was found for failure free survival (p = 0.06) and time to imatinib failure (p = 0.08). In conclusion, our data suggest that a; TP53 c.213 G > C may be a potential biomarker of CML susceptibility and clinical outcome.
Fil: Weich, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Ferri, Cristian Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Moiraghi, Elena Beatriz. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina
Fil: Bengió, Raquel. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Giere, Isabel. Fundaleu; Argentina
Fil: Pavlovsky, Carolina. Fundaleu; Argentina
Fil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Fundia, Ariela Freya. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
description BCR-ABL1 gene is a key molecular marker of chronic myeloid leukemia (CML), but it is still unclear which molecular factors may influence CML risk or lead to variable responses to tyrosine kinase inhibitors (TKIs). The aim of this study was to investigate the impact of TP53 c.213 G > C(Arg72Pro; rs1042522) polymorphism on CML risk and its correlation with clinical outcome. Peripheral blood samples from 141 treated CML patients and 141 sex- and age-matched healthy individuals were genotyped by PCR-RFLP. Standard genetic models for disease penetrance were evaluated by logistic regression analysis and Kaplan-Meier method was performed to estimate survival curves. Our study suggests that TP53 c.213 G > C polymorphism may be involved in CML development considering a recessive model (p = 0.01; OR: 0.19; CI: 0.06–0.68). In addition, a non-homogenous distribution was found for this polymorphism in males and patients youngers than 50 years (p = 0.02). According to clinical response, TP53-GG genotype was associated with higher levels of BCR-ABL1 transcripts (p = 0.04) and shorter event free survival (p = 0.04). Moreover, a trend toward significance was found for failure free survival (p = 0.06) and time to imatinib failure (p = 0.08). In conclusion, our data suggest that a; TP53 c.213 G > C may be a potential biomarker of CML susceptibility and clinical outcome.
publishDate 2016
dc.date.none.fl_str_mv 2016-05
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/11336/39511
Weich, Natalia; Ferri, Cristian Alberto; Moiraghi, Elena Beatriz; Bengió, Raquel; Giere, Isabel; et al.; TP53 codon 72 polymorphism predicts chronic myeloid leukemia susceptibility and treatment outcome; Academic Press Inc Elsevier Science; Blood Cells Molecules And Diseases; 59; 5-2016; 129-133
1079-9796
1096-0961
CONICET Digital
CONICET
url http://hdl.handle.net/11336/39511
identifier_str_mv Weich, Natalia; Ferri, Cristian Alberto; Moiraghi, Elena Beatriz; Bengió, Raquel; Giere, Isabel; et al.; TP53 codon 72 polymorphism predicts chronic myeloid leukemia susceptibility and treatment outcome; Academic Press Inc Elsevier Science; Blood Cells Molecules And Diseases; 59; 5-2016; 129-133
1079-9796
1096-0961
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bcmd.2016.05.007
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1079979616300559
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Academic Press Inc Elsevier Science
publisher.none.fl_str_mv Academic Press Inc Elsevier Science
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
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