TP53-mediated therapy-related clonal hematopoiesis contributes to doxorubicin-induced cardiomyopathy by augmenting a neutrophil-mediated cytotoxic response.
TP53-mediated therapy-related clonal hematopoiesis contributes to doxorubicin-induced cardiomyopathy by augmenting a neutrophil-mediated cytotoxic response.
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DOI：
10.1172/jci.insight.146076
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发表时间：
2021-07-08
期刊：
影响因子：
8
通讯作者：
Walsh K
中科院分区：
文献类型：
--
作者：
Sano S;Wang Y;Ogawa H;Horitani K;Sano M;Polizio AH;Kour A;Yura Y;Doviak H;Walsh K
治疗相关克隆造血（t-CH）经常在癌症幸存者中观察到。这种形式的克隆造血通常涉及编码DNA损伤反应组分的驱动基因的体细胞突变，并赋予造血干细胞和祖细胞（HSPCs）对癌症治疗的遗传毒性应激的抵抗力。在这里，我们通过将Trp53突变的HSPCs转移到小鼠体内，然后用一个疗程的化疗药物阿霉素治疗，建立了tp53介导的t-CH模型。这些研究表明，心脏中性粒细胞浸润显著促进阿霉素诱导的心脏毒性，并且这种情况在trp53介导的t-CH模型中被放大。这些数据表明，在接受基因毒性药物治疗的癌症幸存者中，t-CH可能导致心力衰竭风险升高。
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.
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DOI：
10.1056/nejmoa1409405
发表时间：
2014-12-25
期刊：
The New England journal of medicine
影响因子：
--
作者：
Genovese G;Kähler AK;Handsaker RE;Lindberg J;Rose SA;Bakhoum SF;Chambert K;Mick E;Neale BM;Fromer M;Purcell SM;Svantesson O;Landén M;Höglund M;Lehmann S;Gabriel SB;Moran JL;Lander ES;Sullivan PF;Sklar P;Grönberg H;Hultman CM;McCarroll SA
通讯作者：
McCarroll SA
影响因子：
4.6
作者：
Leong SL;Chaiyakunapruk N;Lee SW
通讯作者：
Lee SW
影响因子：
82.9
作者：
Talukdar, Saswata;Oh, Da Young;Bandyopadhyay, Gautam;Li, Dongmei;Xu, Jianfeng;McNelis, Joanne;Lu, Min;Li, Pingping;Yan, Qingyun;Zhu, Yimin;Ofrecio, Jachelle;Lin, Michael;Brenner, Martin B.;Olefsky, Jerrold M.
通讯作者：
Olefsky, Jerrold M.
影响因子：
24
作者：
Sano S;Oshima K;Wang Y;MacLauchlan S;Katanasaka Y;Sano M;Zuriaga MA;Yoshiyama M;Goukassian D;Cooper MA;Fuster JJ;Walsh K
通讯作者：
Walsh K
TET2功能驱动的克隆造血作用加剧了衰老和肥胖症中的实验性胰岛素抵抗。
影响因子：
8.8
作者：
Fuster JJ;Zuriaga MA;Zorita V;MacLauchlan S;Polackal MN;Viana-Huete V;Ferrer-Pérez A;Matesanz N;Herrero-Cervera A;Sano S;Cooper MA;González-Navarro H;Walsh K
通讯作者：
Walsh K