与治疗相关的克隆性造血的独特景观和临床意义。

IF 13.3 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Koichi Takahashi, Daisuke Nakada, Margaret Goodell
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引用次数: 0

摘要

与治疗相关的克隆性造血(t-CH)是指在曾接受过化疗和/或放疗的患者中发现的克隆性造血。随着基因分析在肿瘤治疗中的应用越来越广泛,在癌症患者中检测到 t-CH 的情况也越来越常见。 t-CH 的产生是由于化疗造成的选择性瓶颈,也可能是化疗的直接诱变,从而导致 DNA 损伤反应通路基因(如 TP53、PPM1D 和 CHEK2)发生突变,形成独特的突变景观。 新的证据揭示了 t-CH 的发展机制以及缓解其出现的潜在策略。由于其主要影响癌症患者的独特特征,t-CH 的临床影响有别于普通人群中的 CH。本综述讨论了 t-CH 发生的潜在机制、突变情况、突变体与药物的关系及其临床意义。我们强调了 t-CH 的独特性,并呼吁加强这一领域的研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Distinct landscape and clinical implications of therapy-related clonal hematopoiesis.

Therapy-related clonal hematopoiesis (t-CH) is defined as clonal hematopoiesis detected in individuals previously treated with chemotherapy and/or radiation therapy. With the increased use of genetic analysis in oncological care, the detection of t-CH among cancer patients is becoming increasingly common. t-CH arises through the selective bottleneck imposed by chemotherapies and potentially through direct mutagenesis from chemotherapies, resulting in a distinct mutational landscape enriched with mutations in DNA damage-response pathway genes such as TP53, PPM1D, and CHEK2. Emerging evidence sheds light on the mechanisms of t-CH development and potential strategies to mitigate its emergence. Due to its unique characteristics that predominantly affect cancer patients, t-CH has clinical implications distinct from those of CH in the general population. This Review discusses the potential mechanisms of t-CH development, its mutational landscape, mutant-drug relationships, and its clinical significance. We highlight the distinct nature of t-CH and call for intensified research in this field.

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来源期刊
Journal of Clinical Investigation
Journal of Clinical Investigation 医学-医学:研究与实验
CiteScore
24.50
自引率
1.30%
发文量
1034
审稿时长
2 months
期刊介绍: The Journal of Clinical Investigation, established in 1924 by the ASCI, is a prestigious publication that focuses on breakthroughs in basic and clinical biomedical science, with the goal of advancing the field of medicine. With an impressive Impact Factor of 15.9 in 2022, it is recognized as one of the leading journals in the "Medicine, Research & Experimental" category of the Web of Science. The journal attracts a diverse readership from various medical disciplines and sectors. It publishes a wide range of research articles encompassing all biomedical specialties, including Autoimmunity, Gastroenterology, Immunology, Metabolism, Nephrology, Neuroscience, Oncology, Pulmonology, Vascular Biology, and many others. The Editorial Board consists of esteemed academic editors who possess extensive expertise in their respective fields. They are actively involved in research, ensuring the journal's high standards of publication and scientific rigor.
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