OnCo
ideasIdea

Which patients' blood clones will become leukaemia after treatment?

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.

Therapy-related myeloid neoplasms follow PPM1D/TP53 clonal haematopoiesis; incidence after PARP inhibitors is ~1-2% and rising with longer use and radioligand therapy.

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.
What would test it
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

Key papers

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observationalNew England Journal of Medicine 2014
Jaiswal: clonal haematopoiesis, the pre-leukaemic clones in most people over 70

Many older people carry blood clones one or two steps from leukaemia, and those clones also drive heart disease through inflammation. CHIP is why blood-based cancer tests must filter out mutations from blood cells, and it opens a route to preventing both leukaemia and cardiovascular events in carriers.

Connected

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Pages like this

not linked directly; found by shared links

cancers

3
Acute myeloid leukaemiaOvarian cancerProstate cancer

technologies

3
Liquid biopsy (ctDNA)PARP inhibitorsRadioligand therapy (beta emitters)

targets

2
PARPTP53

institutions

2
Dana-Farber Brigham Cancer CenterMemorial Sloan Kettering Cancer Center

pathways

2
Clonal haematopoiesis (CHIP)DNA damage response & homologous recombination

key papers

1
Jaiswal: clonal haematopoiesis, the pre-leukaemic clones in most people over 70