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As we age, blood stem cells with cancer-like mutations quietly expand in most people. These clones raise leukaemia and heart disease risk, are accelerated by chemotherapy, and confuse blood tests for cancer DNA.
Clonal haematopoiesis of indeterminate potential (CHIP: DNMT3A, TET2, ASXL1, and after chemotherapy PPM1D, TP53, CHEK2 mutations at VAF ≥2%) is present in >10% of people over 70. It confers ~0.5-1%/year progression to myeloid neoplasm, doubles cardiovascular risk via inflammasome-primed macrophages, and predicts therapy-related MDS/AML after PARP inhibitors, platinum, and radioligand therapy. For liquid biopsy, CHIP variants are the main source of false-positive ctDNA calls, so tumour-informed or paired white-cell sequencing is needed. Interventions are preventive (avoid unnecessary genotoxic exposure, monitor) with IL-1β/IL-6 blockade under study.
Weeds in the blood's seed bank. Harmless individually, they spread with age and after chemical sprays, some turn into leukaemia, and their DNA litters the blood, so a test for tumour DNA can mistake weeds for cancer.
It identifies a way that a good test produces a wrong answer, and it names the fix. Any plasma repair-gene result used to decide on a PARP inhibitor should be run with a paired blood control, or an older man may be treated for a marrow clone rather than for his prostate cancer.
It established plasma profiling as a routine alternative to tissue for the BRCA question in advanced prostate cancer, with a sensible rule attached: if plasma finds nothing actionable, go back to tissue. It also documents at scale both the extra resistance information plasma gives and the clonal haematopoiesis noise that comes with it.
One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
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.
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