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Review
. 2025 Aug;116(8):2055-2063.
doi: 10.1111/cas.70097. Epub 2025 May 19.

Clonal Hematopoiesis and Solid Cancers

Yen T M Nguyen  1 , Manabu Fujisawa  2   3 , Shumpei Ishikawa  4   5 , Mamiko Sakata-Yanagimoto  1   2   6
Affiliations
Review

Clonal Hematopoiesis and Solid Cancers

Yen T M Nguyen et al. Cancer Sci. 2025 Aug.

Abstract

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.

Keywords: TET2 mutations; T‐cell lymphomas; aging; clonal hematopoiesis; solid cancers; tumor microenvironments.

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Conflict of interest statement

The authors declare no conflicts of interest. Dr. Ishikawa, Shumpei and Dr. Sakata‐Yanagimoto, Mamiko, are editorial board members of Cancer Science.

Figures

FIGURE 1
FIGURE 1
Evolution and migration of CH in the human body. CH, clonal hematopoiesis.
FIGURE 2
FIGURE 2
A mechanism of loss‐of‐function Tet2 on lung cancer progression.
See this image and copyright information in PMC

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