# Clonal haematopoiesis (CHIP)

Source: https://onco.cc/pathways/clonal-haematopoiesis/  
OnCo record `clonal-haematopoiesis` (Pathway). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Pathway
- Last checked: 2026-09-08
- Tags: mechanism
- Analogy: 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.
- Interventions: Paired white-blood-cell sequencing in liquid biopsy pipelines; Monitoring after PARP inhibitors and radioligand therapy; IL-1β/IL-6 blockade trials for CHIP-associated cardiovascular risk

## Notes

- Leading programmes: Ebert (Dana-Farber/Broad) and Jaiswal (Stanford) who defined CHIP; Levine and Bolton (MSK) on therapy-related clonal haematopoiesis.
- Prostate cancer: this is where clonal haematopoiesis does concrete harm. In 69 men with advanced prostate cancer, clonal haematopoiesis variants at 2% or more were present in plasma from 13, 19%, and 7, 10%, had one in a gene used to decide PARP inhibitor candidacy, most often ATM, accounting for almost half of all somatic DNA repair variants detected. A paired whole-blood control distinguishes them (Jensen 2021).

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Clonal_hematopoiesis
- Jaiswal et al., Age-related clonal hematopoiesis associated with adverse outcomes (NEJM 2014): https://doi.org/10.1056/NEJMoa1408617
- Bolton et al., Cancer therapy shapes the fitness landscape of clonal hematopoiesis (Nature Genetics 2020): https://doi.org/10.1038/s41588-020-00710-0

## Connected records

- terms: [Ageing tissue and clonal fields: cancer as a disease of old tissue](https://onco.cc/terms/ageing-tissue-field-theory/), [Cell-free DNA (cfDNA)](https://onco.cc/terms/cfdna/), [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [Epigenetic progenitor theory: cancer without a first mutation](https://onco.cc/terms/epigenetic-progenitor-theory/), [From a clone in the blood to a leukaemia: what is known, and what is done](https://onco.cc/terms/rejuv-second-from-clone-to-disease/), [Secondary malignancy (therapy-related cancer)](https://onco.cc/terms/secondary-malignancy/), [Tumour-informed versus tumour-naive ctDNA assays](https://onco.cc/terms/tumour-informed-assay/), [Variant allele frequency (VAF)](https://onco.cc/terms/vaf/)
- cancers: [Acute myeloid leukaemia](https://onco.cc/cancers/aml/), [Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms](https://onco.cc/cancers/cmml/), [Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms](https://onco.cc/cancers/histiocytoses/), [Metastatic castration-resistant prostate cancer](https://onco.cc/cancers/prostate-mcrpc/), [Nodal T-follicular helper cell lymphoma, angioimmunoblastic type (angioimmunoblastic T-cell lymphoma)](https://onco.cc/cancers/angioimmunoblastic-t-cell-lymphoma/), [Prostate cancer](https://onco.cc/cancers/prostate/), [Secondary and therapy-related acute myeloid leukaemia](https://onco.cc/cancers/aml-secondary/), [Systemic mastocytosis](https://onco.cc/cancers/systemic-mastocytosis/)
- technologies: [Clonal haematopoiesis after cancer treatment](https://onco.cc/technologies/rejuv-age-clonal-haematopoiesis-after-therapy/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/), [PARP inhibitors](https://onco.cc/technologies/parp-inhibitor/)
- targets: [ASXL1](https://onco.cc/targets/asxl1/), [B2M](https://onco.cc/targets/b2m/), [CD58](https://onco.cc/targets/cd58/), [DNA methyltransferase 3A (DNMT3A)](https://onco.cc/targets/dnmt3a/), [FYN](https://onco.cc/targets/fyn/), [PARP](https://onco.cc/targets/parp/), [PPM1D](https://onco.cc/targets/ppm1d/), [RHOA](https://onco.cc/targets/rhoa/), [TET2](https://onco.cc/targets/tet2/), [TP53](https://onco.cc/targets/tp53/)
- institutions: [Broad Institute of MIT and Harvard](https://onco.cc/institutions/broad-institute/), [Dana-Farber Brigham Cancer Center](https://onco.cc/institutions/dana-farber/), [Memorial Sloan Kettering Cancer Center](https://onco.cc/institutions/mskcc/)
- pathways: [Clonal evolution & minimal residual disease](https://onco.cc/pathways/clonal-evolution/), [Epigenetic reprogramming](https://onco.cc/pathways/epigenetic-reprogramming/), [Inflammation & NF-κB](https://onco.cc/pathways/inflammation-nfkb/), [Theories of cancer: how the ideas connect](https://onco.cc/pathways/theories-of-cancer/)
- key papers: [Association of clonal haematopoiesis in DNA repair genes with prostate cancer plasma cell-free DNA testing interference](https://onco.cc/key-papers/paper-jensen-clonal-haematopoiesis-cfdna-interference-prostate-jama-oncol-2021/), [Cancer therapy shapes the fitness landscape of clonal hematopoiesis](https://onco.cc/key-papers/paper-bolton-nat-genet/), [Genomic analysis of circulating tumour DNA in 3,334 patients with advanced prostate cancer identifies targetable BRCA alterations and AR resistance mechanisms](https://onco.cc/key-papers/paper-tukachinsky-ctdna-3334-advanced-prostate-ccr-2021/), [Jaiswal: clonal haematopoiesis, the pre-leukaemic clones in most people over 70](https://onco.cc/key-papers/paper-jaiswal-chip-nejm-2014/)
- biomarkers: [Circulating tumour DNA fraction (and what a negative plasma result means)](https://onco.cc/biomarkers/ctdna-tumour-fraction/), [RHOA G17V](https://onco.cc/biomarkers/rhoa-g17v/)
- ideas: [Which patients' blood clones will become leukaemia after treatment?](https://onco.cc/ideas/idea-chip-risk-modifiers/)
- roadmaps: [ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment](https://onco.cc/roadmaps/ctdna-tests/)

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