TP53-mediated therapy-related clonal hematopoiesis contributes to doxorubicin-induced cardiomyopathy by augmenting a neutrophil-mediated cytotoxic response

Autores
Sano, Soichi; Wang, Ying; Ogawa, Hayato; Horitani, Keita; Sano, Miho; Polizio, Ariel Héctor; Kour, Anupreet; Yoshimitsu, Yura; Doviak, Heather; Walsh, Kenneth
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Therapy-related clonal hematopoiesis (t-CH) is often observed in cancer survivors. This form of clonal hematopoiesis typically involves somatic mutations in driver genes that encode components of the DNA damage response and confer hematopoietic stem and progenitor cells (HSPCs) with resistance to the genotoxic stress of the cancer therapy. Here, we established a model of TP53-mediated t-CH through the transfer of Trp53 mutant HSPCs to mice, followed by treatment with a course of the chemotherapeutic agent doxorubicin. These studies revealed that neutrophil infiltration in the heart significantly contributes to doxorubicin-induced cardiac toxicity and that this condition is amplified in the model of Trp53-mediated t-CH. These data suggest that t-CH could contribute to the elevated heart failure risk that occurs in cancer survivors who have been treated with genotoxic agents.
Fil: Sano, Soichi. University of Virginia; Estados Unidos
Fil: Wang, Ying. University of Virginia; Estados Unidos
Fil: Ogawa, Hayato. University of Virginia; Estados Unidos
Fil: Horitani, Keita. University of Virginia; Estados Unidos
Fil: Sano, Miho. University of Virginia; Estados Unidos
Fil: Polizio, Ariel Héctor. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Kour, Anupreet. University of Virginia; Estados Unidos
Fil: Yoshimitsu, Yura. University of Virginia; Estados Unidos
Fil: Doviak, Heather. University of Virginia; Estados Unidos
Fil: Walsh, Kenneth. University of Virginia; Estados Unidos
Materia
Cardiology
Cardiovascular disease
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:11336/164017
Acceder
id CONICETDig_dce232ae8afbc4584ca76a535a2b52e0
oai_identifier_str oai:ri.conicet.gov.ar:11336/164017
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling TP53-mediated therapy-related clonal hematopoiesis contributes to doxorubicin-induced cardiomyopathy by augmenting a neutrophil-mediated cytotoxic responseSano, SoichiWang, YingOgawa, HayatoHoritani, KeitaSano, MihoPolizio, Ariel HéctorKour, AnupreetYoshimitsu, YuraDoviak, HeatherWalsh, KennethCardiologyCardiovascular diseasehttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Therapy-related clonal hematopoiesis (t-CH) is often observed in cancer survivors. This form of clonal hematopoiesis typically involves somatic mutations in driver genes that encode components of the DNA damage response and confer hematopoietic stem and progenitor cells (HSPCs) with resistance to the genotoxic stress of the cancer therapy. Here, we established a model of TP53-mediated t-CH through the transfer of Trp53 mutant HSPCs to mice, followed by treatment with a course of the chemotherapeutic agent doxorubicin. These studies revealed that neutrophil infiltration in the heart significantly contributes to doxorubicin-induced cardiac toxicity and that this condition is amplified in the model of Trp53-mediated t-CH. These data suggest that t-CH could contribute to the elevated heart failure risk that occurs in cancer survivors who have been treated with genotoxic agents.Fil: Sano, Soichi. University of Virginia; Estados UnidosFil: Wang, Ying. University of Virginia; Estados UnidosFil: Ogawa, Hayato. University of Virginia; Estados UnidosFil: Horitani, Keita. University of Virginia; Estados UnidosFil: Sano, Miho. University of Virginia; Estados UnidosFil: Polizio, Ariel Héctor. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Kour, Anupreet. University of Virginia; Estados UnidosFil: Yoshimitsu, Yura. University of Virginia; Estados UnidosFil: Doviak, Heather. University of Virginia; Estados UnidosFil: Walsh, Kenneth. University of Virginia; Estados UnidosAmerican Society for Clinical Investigation2021-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/164017Sano, Soichi; Wang, Ying; Ogawa, Hayato; Horitani, Keita; Sano, Miho; et al.; TP53-mediated therapy-related clonal hematopoiesis contributes to doxorubicin-induced cardiomyopathy by augmenting a neutrophil-mediated cytotoxic response; American Society for Clinical Investigation; JCI Insight; 6; 13; 7-2021; 1-112379-3708CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://insight.jci.org/articles/view/146076info:eu-repo/semantics/altIdentifier/doi/10.1172/jci.insight.146076info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-08-25T15:04:38Zoai:ri.conicet.gov.ar:11336/164017instacron: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:34982026-08-25 15:04:39.052CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv TP53-mediated therapy-related clonal hematopoiesis contributes to doxorubicin-induced cardiomyopathy by augmenting a neutrophil-mediated cytotoxic response
title TP53-mediated therapy-related clonal hematopoiesis contributes to doxorubicin-induced cardiomyopathy by augmenting a neutrophil-mediated cytotoxic response
spellingShingle TP53-mediated therapy-related clonal hematopoiesis contributes to doxorubicin-induced cardiomyopathy by augmenting a neutrophil-mediated cytotoxic response
Sano, Soichi
Cardiology
Cardiovascular disease
title_short TP53-mediated therapy-related clonal hematopoiesis contributes to doxorubicin-induced cardiomyopathy by augmenting a neutrophil-mediated cytotoxic response
title_full TP53-mediated therapy-related clonal hematopoiesis contributes to doxorubicin-induced cardiomyopathy by augmenting a neutrophil-mediated cytotoxic response
title_fullStr TP53-mediated therapy-related clonal hematopoiesis contributes to doxorubicin-induced cardiomyopathy by augmenting a neutrophil-mediated cytotoxic response
title_full_unstemmed TP53-mediated therapy-related clonal hematopoiesis contributes to doxorubicin-induced cardiomyopathy by augmenting a neutrophil-mediated cytotoxic response
title_sort TP53-mediated therapy-related clonal hematopoiesis contributes to doxorubicin-induced cardiomyopathy by augmenting a neutrophil-mediated cytotoxic response
dc.creator.none.fl_str_mv Sano, Soichi
Wang, Ying
Ogawa, Hayato
Horitani, Keita
Sano, Miho
Polizio, Ariel Héctor
Kour, Anupreet
Yoshimitsu, Yura
Doviak, Heather
Walsh, Kenneth
author Sano, Soichi
author_facet Sano, Soichi
Wang, Ying
Ogawa, Hayato
Horitani, Keita
Sano, Miho
Polizio, Ariel Héctor
Kour, Anupreet
Yoshimitsu, Yura
Doviak, Heather
Walsh, Kenneth
author_role author
author2 Wang, Ying
Ogawa, Hayato
Horitani, Keita
Sano, Miho
Polizio, Ariel Héctor
Kour, Anupreet
Yoshimitsu, Yura
Doviak, Heather
Walsh, Kenneth
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cardiology
Cardiovascular disease
topic Cardiology
Cardiovascular disease
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Therapy-related clonal hematopoiesis (t-CH) is often observed in cancer survivors. This form of clonal hematopoiesis typically involves somatic mutations in driver genes that encode components of the DNA damage response and confer hematopoietic stem and progenitor cells (HSPCs) with resistance to the genotoxic stress of the cancer therapy. Here, we established a model of TP53-mediated t-CH through the transfer of Trp53 mutant HSPCs to mice, followed by treatment with a course of the chemotherapeutic agent doxorubicin. These studies revealed that neutrophil infiltration in the heart significantly contributes to doxorubicin-induced cardiac toxicity and that this condition is amplified in the model of Trp53-mediated t-CH. These data suggest that t-CH could contribute to the elevated heart failure risk that occurs in cancer survivors who have been treated with genotoxic agents.
Fil: Sano, Soichi. University of Virginia; Estados Unidos
Fil: Wang, Ying. University of Virginia; Estados Unidos
Fil: Ogawa, Hayato. University of Virginia; Estados Unidos
Fil: Horitani, Keita. University of Virginia; Estados Unidos
Fil: Sano, Miho. University of Virginia; Estados Unidos
Fil: Polizio, Ariel Héctor. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Kour, Anupreet. University of Virginia; Estados Unidos
Fil: Yoshimitsu, Yura. University of Virginia; Estados Unidos
Fil: Doviak, Heather. University of Virginia; Estados Unidos
Fil: Walsh, Kenneth. University of Virginia; Estados Unidos
description Therapy-related clonal hematopoiesis (t-CH) is often observed in cancer survivors. This form of clonal hematopoiesis typically involves somatic mutations in driver genes that encode components of the DNA damage response and confer hematopoietic stem and progenitor cells (HSPCs) with resistance to the genotoxic stress of the cancer therapy. Here, we established a model of TP53-mediated t-CH through the transfer of Trp53 mutant HSPCs to mice, followed by treatment with a course of the chemotherapeutic agent doxorubicin. These studies revealed that neutrophil infiltration in the heart significantly contributes to doxorubicin-induced cardiac toxicity and that this condition is amplified in the model of Trp53-mediated t-CH. These data suggest that t-CH could contribute to the elevated heart failure risk that occurs in cancer survivors who have been treated with genotoxic agents.
publishDate 2021
dc.date.none.fl_str_mv 2021-07
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/11336/164017
Sano, Soichi; Wang, Ying; Ogawa, Hayato; Horitani, Keita; Sano, Miho; et al.; TP53-mediated therapy-related clonal hematopoiesis contributes to doxorubicin-induced cardiomyopathy by augmenting a neutrophil-mediated cytotoxic response; American Society for Clinical Investigation; JCI Insight; 6; 13; 7-2021; 1-11
2379-3708
CONICET Digital
CONICET
url http://hdl.handle.net/11336/164017
identifier_str_mv Sano, Soichi; Wang, Ying; Ogawa, Hayato; Horitani, Keita; Sano, Miho; et al.; TP53-mediated therapy-related clonal hematopoiesis contributes to doxorubicin-induced cardiomyopathy by augmenting a neutrophil-mediated cytotoxic response; American Society for Clinical Investigation; JCI Insight; 6; 13; 7-2021; 1-11
2379-3708
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://insight.jci.org/articles/view/146076
info:eu-repo/semantics/altIdentifier/doi/10.1172/jci.insight.146076
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 American Society for Clinical Investigation
publisher.none.fl_str_mv American Society for Clinical Investigation
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_ 1874775110383042560
score 13.365483

Publicaciones similares