Nguyen Yen T M, Fujisawa Manabu, Ishikawa Shumpei, Sakata-Yanagimoto Mamiko
Department of Hematology, University of Tsukuba Hospital, University of Tsukuba, Tsukuba, Japan.
Department of Hematology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
Cancer Sci. 2025 Aug;116(8):2055-2063. doi: 10.1111/cas.70097. Epub 2025 May 19.
Clonal hematopoiesis refers to the expansion of hematopoietic stem cells harboring somatic mutations, a phenomenon increasingly recognized in aging populations. This review highlights the emerging relationship between clonal hematopoiesis and solid cancers, focusing on the prevalence and impact of clonal hematopoiesis-associated mutations such as DNMT3A, TET2, ASXL1, and TP53 in tumorigenesis. Key risk factors for the co-occurrence of clonal hematopoiesis and solid cancers, including germline genetic factors, aging, and environmental factors, are also discussed. We explore how clonal hematopoiesis mutations shape the tumor microenvironments in solid cancers by modulating immunoregulation, inflammation, and angiogenesis, thereby contributing to tumor progression. These findings underscore the dual role of clonal hematopoiesis as both a marker of cancer risk and a potential driver of solid cancer progression. The clinical implications of clonal hematopoiesis are also considered, including the prognostic value, impact on treatment response, and potential as a therapeutic target. Future directions are outlined to advance our understanding of clonal hematopoiesis and to exploit its clinical potential for cancer management.
克隆性造血是指携带体细胞突变的造血干细胞的扩增，这一现象在老年人群中越来越受到关注。本综述重点介绍了克隆性造血与实体癌之间新出现的关系，着重探讨了与克隆性造血相关的突变（如DNMT3A、TET2、ASXL1和TP53）在肿瘤发生中的发生率和影响。还讨论了克隆性造血与实体癌同时发生的关键风险因素，包括种系遗传因素、衰老和环境因素。我们探讨了克隆性造血突变如何通过调节免疫调节、炎症和血管生成来塑造实体癌的肿瘤微环境，从而促进肿瘤进展。这些发现强调了克隆性造血作为癌症风险标志物和实体癌进展潜在驱动因素的双重作用。还考虑了克隆性造血的临床意义，包括预后价值、对治疗反应的影响以及作为治疗靶点的潜力。概述了未来的研究方向，以增进我们对克隆性造血的理解，并挖掘其在癌症管理中的临床潜力。
