# Which patients' blood clones will become leukaemia after treatment?

Source: https://onco.cc/ideas/idea-chip-risk-modifiers/  
OnCo record `idea-chip-risk-modifiers` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Tags: mechanism; open-question
- 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.
- Proposed 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

## Sources

- Jaiswal: clonal haematopoiesis, the pre-leukaemic clones in most people over 70 (New England Journal of Medicine 2014): https://doi.org/10.1056/NEJMoa1408617

## Connected records

- cancers: [Acute myeloid leukaemia](https://onco.cc/cancers/aml/), [Ovarian cancer](https://onco.cc/cancers/ovarian/), [Prostate cancer](https://onco.cc/cancers/prostate/), [Secondary and therapy-related acute myeloid leukaemia](https://onco.cc/cancers/aml-secondary/)
- technologies: [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [PARP inhibitors](https://onco.cc/technologies/parp-inhibitor/), [Radioligand therapy (beta emitters)](https://onco.cc/technologies/radioligand-therapy/)
- targets: [PARP](https://onco.cc/targets/parp/), [TP53](https://onco.cc/targets/tp53/)
- institutions: [Dana-Farber Brigham Cancer Center](https://onco.cc/institutions/dana-farber/), [Memorial Sloan Kettering Cancer Center](https://onco.cc/institutions/mskcc/)
- pathways: [Clonal haematopoiesis (CHIP)](https://onco.cc/pathways/clonal-haematopoiesis/), [DNA damage response & homologous recombination](https://onco.cc/pathways/ddr/)
- key papers: [Jaiswal: clonal haematopoiesis, the pre-leukaemic clones in most people over 70](https://onco.cc/key-papers/paper-jaiswal-chip-nejm-2014/), [Vogelstein, Lane and Levine 2000: surfing the p53 network](https://onco.cc/key-papers/paper-vogelstein-surfing-p53-network-nature-2000/)

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