Clonal hematopoiesis in patients with cancer and cancer survivors - From clonal burden to cardiovascular diseases

Sep 22, 2026

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Over the past decade, clonal hematopoiesis (CH) has become widely recognized as a prevalent, age-associated condition with major implications for hematologic malignancy, cardiovascular disease, and mortality. CH results from clonal expansion of hematopoietic stem and progenitor cells carrying somatic mutations, often in leukemia-linked genes. In addition to aging and chronic stressors, cancer therapies—especially cytotoxic treatments—raise CH risk, typically via a distinct DNA damage response mutational spectrum that expands preexisting clones. CH is associated with worse survival in many cancer patients and with increased cardiovascular risk, relevant to survivorship and precision oncology.

LanguageEnglish

CategoryHealthcare

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Abstract

Introduction

DOI: 10. 1002/cncr.70444 REVIEW ARTICLE Clonal hematopoiesis in patients with cancer and cancer survivors: From clonal burden to cardiovascular diseases Christian H. Nenninger BS1,2 | Keith Anderson BS2 | Jenaro Espitia-Corredor PhD3 | Brittany Echevarria BS2 | Vertica Agnihotri PhD2 | Zhao Wang PhD3 | Scott R. Goldsmith MD4 | June-Wha Rhee MD2 1 Irell and Manella Graduate School of Biological Sciences, City of Hope National Medical Center, Duarte, California, USA 2Division of Cardiology, Department of Medicine, Beckman Research Institute, City of Hope National Medical Center, Duarte, California, USA 3Department of Diabetes and Cancer Metabolism, Beckman Research Institute, City of Hope National Medical Center, Duarte, California, USA 4Division of Multiple Myeloma, Department of Hematology and Hematopoietic Transplantation, City of Hope National Medical Center, Duarte, California, USA Correspondence June-Wha Rhee, Department of Medicine, City of Hope Comprehensive Cancer Center, 1500 East Duarte Road, Duarte, CA 91010, USA. Email: [jrhee@coh.org](jrhee@coh.org) Scott R. Goldsmith, Department of Hematology and Hematopoietic Transplantation, City of Hope Comprehensive Cancer Center, 1500 East Duarte Road, Duarte, CA 91010, USA. Email: [sgoldsmith@coh.org](sgoldsmith@coh.org) ABSTRACT Over the past decade, clonal hematopoiesis (CH) has gained substantial attention asa prevalent, age-associated phenomenon with major implications for hematologic malignancy, cardiovascular disease, and mortality. CH arises from the clonal expansion of hematopoietic stem cells and progenitor cells harboring somatic mutations, most commonly in genes implicated in leukemia. Beyond chronological aging, CH evolution is shaped by lifelong exposure to inflammatory, metabolic, and environmental stressors, such as smoking and obesity. More recently, cancer therapies—particularly cytotoxic treatments—have been shown to significantly increase the risk of CH. Therapy-related CH, however, exhibits a distinct mutational spectrum, frequently involving genes in the DNA damage response pathway, reflecting the selective pressure exerted by cytotoxic exposure. Current evidence largely supports that cytotoxic therapies primarily drive the expansion of preexisting mutant clones rather than inducing de novo mutations. The increased recognition of therapy-related CH has prompted growing interest in its prognostic and therapeutic implications in patients with cancer. To date, data regarding the prognostic impact of CH in cancer are conflicting, but the presence of CH generally portends worse overall survival, especially among patients with hematologic malignancies. Moreover, cancer survivors with CH appear to be at a heightened risk of cardiovascular disease, which may be further exacerbated by exposure to cardiotoxic cancer therapies. Collectively, these findings underscore the growing clinical relevance of CH and highlight its potential implications for precision medicine and survivorship care in oncology. KEYWORDS cancer, cardiovascular disease, clonal hematopoiesis, therapy This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2026 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society. Cancer. 2026;e70444. [https://doi.org/10.1002/cncr.70444](https://doi.org/10.1002/cncr.70444) wi[leyonlinelibrary.com/journal/cncr](leyonlinelibrary.com/journal/cncr) 1 of 11 INTRODUCTION Clonal hematopoiesis (CH) refers to the clonal expansion of hematopoietic stem cells (HSCs) and/or their progeny in the absence of overthematologic malignancy, typically driven by somatic mutations. CH was first identified through observations of age-associated skewing in X-inactivation in

FAQs

What is clonal hematopoiesis (CH) and how does it develop?

CH is the clonal expansion of hematopoietic stem cells and/or their progeny driven by somatic mutations. It can occur in the absence of overt hematologic malignancy.

How do aging and environmental stressors contribute to CH?

Beyond chronological aging, CH evolution is influenced by lifelong exposure to inflammatory, metabolic, and environmental stressors such as smoking and obesity.

What is the relationship between cancer therapy and CH?

Cancer therapies, particularly cytotoxic treatments, increase CH risk. The therapy-related form often shows a distinct mutational spectrum, frequently involving DNA damage response pathways, and evidence suggests expansion of preexisting mutant clones rather than widespread de novo mutation.

Sep 22, 2026

Uploaded by Bintang