Over the past decade, clonal hematopoiesis (CH) has gained substantial attention as a 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.
Nenninger et al. (2026) studied this question.