{"doi":"10.1101/2025.08.27.25334581","title":"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, PPM1D, SRCAP, DNMT3A, and YLPM1. Patients with positively selected CH during treatment had the shortest progression-free and overall survival compared to patients with unchanging or negatively selected CH across all therapies. These findings, corroborated in independent breast cancer and pan-cancer cohorts, provide strong evidence for clinical relevance of changes in CH during cancer treatment which may help identify patients at high risk for inferior outcomes.","journal":"medRxiv","year":2025,"id":556719,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9525,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1260034,"name":"Yi-Han Tang","orcid":"0009-0006-2248-1978","position":1,"is_corresponding":false},{"id":362030,"name":"Christelle Colin","orcid":"0000-0002-8118-9591","position":2,"is_corresponding":false},{"id":1456387,"name":"Sadegh Marzban","orcid":"0000-0002-9435-017X","position":3,"is_corresponding":false},{"id":1456798,"name":"Daniel Walgenbach","orcid":null,"position":4,"is_corresponding":false},{"id":1456388,"name":"Stefania Morganti","orcid":"0000-0001-5284-9944","position":5,"is_corresponding":false},{"id":584257,"name":"Vaidhyanathan Mahaganapathy","orcid":"0000-0003-0577-2870","position":6,"is_corresponding":false},{"id":1456799,"name":"Erika Harper","orcid":null,"position":7,"is_corresponding":false},{"id":43177,"name":"Mingxiang Teng","orcid":"0000-0002-8536-8941","position":8,"is_corresponding":false},{"id":275134,"name":"Jacob K. Kresovich","orcid":"0000-0002-9577-226X","position":9,"is_corresponding":false},{"id":1379454,"name":"Iman Washington","orcid":"0000-0003-2118-9634","position":10,"is_corresponding":false},{"id":38073,"name":"Heather A. Parsons","orcid":"0000-0001-8178-6612","position":11,"is_corresponding":false},{"id":95411,"name":"Judy E. Garber","orcid":"0000-0001-9449-3982","position":12,"is_corresponding":false},{"id":280728,"name":"Jeffrey West","orcid":"0000-0001-9579-4664","position":13,"is_corresponding":false},{"id":448,"name":"Shridar Ganesan","orcid":"0000-0002-5404-3044","position":14,"is_corresponding":false},{"id":491652,"name":"Hossein Khiabanian","orcid":"0000-0003-1446-4394","position":15,"is_corresponding":false},{"id":108816,"name":"Nancy Gillis","orcid":"0000-0002-7744-8490","position":16,"is_corresponding":false},{"id":1456797,"name":"Mona Arabzadeh","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:55:13.130091Z","pmid":"40950448","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}