Clonal haematopoiesis: a major link in the cancer–Alzheimer's disease inverse correlation eBioMedicine (+...)

Clonal haematopoiesis: a major link in the cancer–Alzheimer's disease inverse correlation eBioMedicine https://www.thelancet.com/journals/ebiom/issue/vol133nonull/PIIS2352-3964(26)X2009-6 First characterised in 2014, clonal haematopoiesis is a condition defined by the expansion of a haematopoietic stem cell clone, and its progeny, carrying somatic mutations in leukaemia-associated genes. Sensitive sequencing techniques show that clonal haematopoiesis, irrespective of clone size, becomes near-universal with ageing. A related term, clonal haematopoiesis of indeterminate potential (CHIP), describes the presence of a clone that has expanded to a variant allele fraction of ≥2% (and as a result ≥4% of nucleated blood cells) and is considered clinically significant. As expected, CHIP is a strong risk factor for subsequent haematologic cancers (hazard ratio 12·9 [95% CI 5·8–28·7]). Incident coronary heart disease (2·0 [1·2–3·4]), ischaemic stroke (2·6 [1·4–4·8]), and all-cause mortality (1·4 [1·1–1·8]) also increased. Mechanistic studies in animal models suggest that altered gene expression and changes in the function of circulating mutant macrophages are likely to contribute to the more rapid expansion of atherosclerotic lesions in the presence of CHIP.