{"entity":{"id":"rejuv-age-clonal-haematopoiesis-after-therapy","kind":"technology","name":"Clonal haematopoiesis after cancer treatment","aka":[],"tldr":"Chemotherapy and radiotherapy do not select blood stem cells at random. They favour the ones carrying mutations in DNA-damage genes, which then expand. Most people with such a clone never develop a blood cancer, but the clone is a measurable mark of what treatment did, and in a minority it is the seed of a later leukaemia.","summary":"Clonal haematopoiesis is the expansion of a blood stem cell carrying a somatic mutation. It is common with age and more common after cancer treatment. In 8,810 people with non-haematologic cancers sequenced on paired tumour and blood samples, clonal haematopoiesis was found in 25 per cent, and 4.5 per cent carried a presumptive leukaemia driver mutation. It was associated with older age, prior radiotherapy and tobacco use; PPM1D and TP53 mutations were associated with prior chemotherapy. Carriers had a higher incidence of a subsequent blood cancer, and those with a driver mutation had shorter survival.\n\nA second study showed the selection directly. Mutations in ASXL1 were enriched in smokers and former smokers, while radiotherapy, platinum drugs and topoisomerase II inhibitors preferentially selected mutations in the DNA damage response genes TP53, PPM1D and CHEK2. Sequential samples from the same people showed those clones outcompeting others once the exposure arrived. Where clonal haematopoiesis had been detected before a therapy-related myeloid neoplasm appeared, the same mutation was present at diagnosis of the neoplasm.\n\nThis matters to a reader for three reasons. It is a measurable, mechanistic trace of treatment on a stem cell compartment, not an inference from a questionnaire. It explains part of the second-cancer risk that survivorship follow-up is designed to catch. And it is a reason to be cautious about anything sold as 'resetting' or 'boosting' blood stem cells: the clones that treatment selected for are the ones with a fitness advantage.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Clonal_hematopoiesis","links":[{"label":"Coombs et al., Therapy-related clonal hematopoiesis in patients with non-hematologic cancers is common and associated with adverse clinical outcomes (Cell Stem Cell 2017)","url":"https://doi.org/10.1016/j.stem.2017.07.010"},{"label":"Bolton et al., Cancer therapy shapes the fitness landscape of clonal hematopoiesis (Nat Genet 2020)","url":"https://doi.org/10.1038/s41588-020-00710-0"}],"tags":["rejuvenation","survivorship","biological-ageing","blood","second-cancers"],"related":["rejuv-age-epigenetic-clocks","rejuv-age-frailty-and-late-effects","rejuv-frontier-what-works"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["survivorship-care-plan","second-cancers-after-radiotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["clonal-haematopoiesis"],"terms":["late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Cytotoxic therapy imposes selection on haematopoietic stem cells. Clones with loss-of-function or dominant-negative mutations in the p53 pathway survive genotoxic stress better than their neighbours, so the exposure that damages the marrow also changes which clones repopulate it.","strengths":["Measured directly by deep sequencing of blood, with paired samples before and after exposure","Links a specific drug or radiation exposure to a specific mutational signature","Identifies a group at higher risk of therapy-related myeloid neoplasm for surveillance"],"limitations":["Most carriers never develop a blood cancer, so the finding is not a diagnosis","No intervention has been shown to clear a clone or reduce the risk it carries","Testing outside a research setting can produce a result nobody knows how to act on"]},"route":"/technologies/rejuv-age-clonal-haematopoiesis-after-therapy/","neighbours":{"technology":[{"id":"rejuv-tx-prolonged-cytopenias","kind":"technology","name":"Blood counts that do not come back after CAR-T: ICAHT","route":"/technologies/rejuv-tx-prolonged-cytopenias/"},{"id":"rejuv-age-epigenetic-clocks","kind":"technology","name":"Epigenetic age after cancer treatment","route":"/technologies/rejuv-age-epigenetic-clocks/"},{"id":"rejuv-age-frailty-and-late-effects","kind":"technology","name":"Frailty and late effects in survivors","route":"/technologies/rejuv-age-frailty-and-late-effects/"},{"id":"rejuv-tx-second-cancers","kind":"technology","name":"Second cancers after allogeneic transplant","route":"/technologies/rejuv-tx-second-cancers/"},{"id":"rejuv-tx-secondary-t-cell-malignancy","kind":"technology","name":"Secondary T-cell malignancy after CAR-T, and what the FDA's 2024 action actually says","route":"/technologies/rejuv-tx-secondary-t-cell-malignancy/"},{"id":"survivorship-care-plan","kind":"technology","name":"Survivorship care and late-effects surveillance","route":"/technologies/survivorship-care-plan/"},{"id":"rejuv-age-telomere-length","kind":"technology","name":"Telomere length after treatment","route":"/technologies/rejuv-age-telomere-length/"},{"id":"rejuv-frontier-what-works","kind":"technology","name":"What actually works after treatment","route":"/technologies/rejuv-frontier-what-works/"}],"section":[{"id":"rejuvenation","kind":"section","name":"Recovery & Rejuvenation","route":"/fronts/rejuvenation/"},{"id":"supportive-care","kind":"section","name":"Supportive Care & Survivorship","route":"/fronts/supportive-care/"}],"term":[{"id":"rejuv-second-alkylating-agents-and-myeloid-neoplasms","kind":"term","name":"Alkylating agents and therapy-related myeloid neoplasms","route":"/terms/rejuv-second-alkylating-agents-and-myeloid-neoplasms/"},{"id":"rejuv-second-from-clone-to-disease","kind":"term","name":"From a clone in the blood to a leukaemia: what is known, and what is done","route":"/terms/rejuv-second-from-clone-to-disease/"},{"id":"late-effects","kind":"term","name":"Late effects and survivorship toxicity","route":"/terms/late-effects/"},{"id":"second-cancers-after-radiotherapy","kind":"term","name":"Second cancers after radiotherapy","route":"/terms/second-cancers-after-radiotherapy/"}],"pathway":[{"id":"clonal-haematopoiesis","kind":"pathway","name":"Clonal haematopoiesis (CHIP)","route":"/pathways/clonal-haematopoiesis/"}],"bottleneck":[{"id":"b-survivorship","kind":"bottleneck","name":"Survivorship and late effects are neglected","route":"/bottlenecks/b-survivorship/"}]}}