Clonal hematopoiesis (CHIP)

Clonal hematopoiesis of indeterminate potential (CHIP) refers to the somatic expansion of a hematopoietic stem cell clone carrying a driver mutation — most commonly in DNMT3A, TET2, ASXL1, or JAK2 — in the blood of individuals without overt haematologic malignancy. The prevalence rises sharply with age, reaching roughly 10–20% in people over 70. Landmark analyses by Jaiswal and colleagues (2017) demonstrated that CHIP carriers have approximately double the risk of cardiovascular events, a finding attributed partly to pro-inflammatory macrophage programming by TET2-mutant clones. Because CHIP alters the epigenetic and transcriptional landscape of blood cells, it confounds DNA-methylation-based biological age clocks and other blood-based aging biomarkers, representing an important caveat in their interpretation.