Artículo
TP53-mediated therapy-related clonal hematopoiesis contributes to doxorubicin-induced cardiomyopathy by augmenting a neutrophil-mediated cytotoxic response
Sano, Soichi; Wang, Ying; Ogawa, Hayato; Horitani, Keita; Sano, Miho; Polizio, Ariel Héctor
; Kour, Anupreet; Yoshimitsu, Yura; Doviak, Heather; Walsh, Kenneth
![Icon](/themes/CONICETDigital/images/conicet.png)
Fecha de publicación:
07/2021
Editorial:
American Society for Clinical Investigation
Revista:
JCI Insight
ISSN:
2379-3708
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
Palabras clave:
Cardiology
,
Cardiovascular disease
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Articulos(OCA HOUSSAY)
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Citación
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
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