{"entity":{"id":"idea-chip-risk-modifiers","kind":"idea","name":"Which patients' blood clones will become leukaemia after treatment?","aka":[],"tldr":"PARP inhibitors, platinum, and radioligand drugs can push pre-existing blood-cell clones toward leukaemia in a few patients. Predicting who could let us choose therapies more safely.","summary":"This open question asks which patients' blood clones will become leukaemia after treatment: PARP inhibitors, platinum and radioligand drugs push pre-existing clones toward leukaemia in a few patients. Therapy-related myeloid neoplasms follow PPM1D and TP53 clonal haematopoiesis; incidence after PARP inhibitors is low but rising with longer use and Radioligand therapy (beta emitters), see Clonal haematopoiesis (CHIP). The hypothesis is that baseline CHIP genotype and variant allele fraction, with the planned genotoxic exposure, predict therapy-related MDS and AML well enough to guide drug choice and monitoring (Bolton 2020). The test is a prospective registry with baseline CHIP sequencing before these therapies, relevant to Acute myeloid leukaemia, Ovarian cancer and Prostate cancer.","asOf":"2026-09-08","links":[{"label":"Jaiswal: clonal haematopoiesis, the pre-leukaemic clones in most people over 70 (New England Journal of Medicine 2014)","url":"https://doi.org/10.1056/NEJMoa1408617"}],"tags":["mechanism","open-question"],"related":[],"cancers":["aml","ovarian","prostate"],"sections":[],"technologies":["parp-inhibitor","radioligand-therapy","liquid-biopsy"],"targets":["parp","tp53"],"drugs":[],"companies":[],"institutions":["dana-farber","mskcc"],"pathways":["clonal-haematopoiesis","ddr"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-vogelstein-surfing-p53-network-nature-2000"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Baseline CHIP genotype and VAF, combined with the planned genotoxic exposure, predicts therapy-related MDS/AML well enough to guide drug choice and monitoring.","rationale":"Bolton 2020 described the fitness landscapes of these clones under therapy, and the populations on long-term PARP inhibitors and 177Lu therapies are growing.","test":"Prospective registry with baseline CHIP sequencing in patients starting PARP inhibitors or radioligand therapy, validating a risk score; randomised monitoring intensity trial.","maturity":"preclinical-evidence"},"route":"/ideas/idea-chip-risk-modifiers/","neighbours":{"cancer":[{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"aml-secondary","kind":"cancer","name":"Secondary and therapy-related acute myeloid leukaemia","route":"/cancers/aml-secondary/"}],"technology":[{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"},{"id":"parp-inhibitor","kind":"technology","name":"PARP inhibitors","route":"/technologies/parp-inhibitor/"},{"id":"radioligand-therapy","kind":"technology","name":"Radioligand therapy (beta emitters)","route":"/technologies/radioligand-therapy/"}],"target":[{"id":"parp","kind":"target","name":"PARP","route":"/targets/parp/"},{"id":"tp53","kind":"target","name":"TP53","route":"/targets/tp53/"}],"institution":[{"id":"dana-farber","kind":"institution","name":"Dana-Farber Brigham Cancer Center","route":"/institutions/dana-farber/"},{"id":"mskcc","kind":"institution","name":"Memorial Sloan Kettering Cancer Center","route":"/institutions/mskcc/"}],"pathway":[{"id":"clonal-haematopoiesis","kind":"pathway","name":"Clonal haematopoiesis (CHIP)","route":"/pathways/clonal-haematopoiesis/"},{"id":"ddr","kind":"pathway","name":"DNA damage response & homologous recombination","route":"/pathways/ddr/"}],"paper":[{"id":"paper-jaiswal-chip-nejm-2014","kind":"paper","name":"Jaiswal: clonal haematopoiesis, the pre-leukaemic clones in most people over 70","route":"/key-papers/paper-jaiswal-chip-nejm-2014/"},{"id":"paper-vogelstein-surfing-p53-network-nature-2000","kind":"paper","name":"Vogelstein, Lane and Levine 2000: surfing the p53 network","route":"/key-papers/paper-vogelstein-surfing-p53-network-nature-2000/"}]}}