Clonal Hematopoiesis Dynamics and Evolutionary Fitness During Cancer Treatment Impact Clinical Outcomes.

ABSTRACT: Clonal hematopoiesis (CH) is the age-related expansion of mutated hematopoietic stem cells without other hematologic abnormalities. In patients with solid tumors, CH is associated with higher mortality and may evolve to therapy-related myeloid neoplasms; however, the mechanisms by which cancer treatments promote CH dynamics remain largely unknown. Here, we analyzed 392 serial samples from a prospective cohort of breast cancer patients and showed that cytotoxic treatments (chemotherapy ± radiation) led to strong therapeutic bottlenecks, resulting in significant reductions in hematopoietic allelic populations and differential clonal selection. CH clones that were positively selected and expanded through dose-dependent therapeutic bottlenecks frequently harbored mutations in TP53, P

SUBMITTER: Arabzadeh M 

PROVIDER: S-EPMC12424905 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature