Clonal hematopoiesis of indeterminate potential: contribution to disease and promising interventions

Abstract

In clonal hematopoiesis of indeterminate potential (CHIP), subpopulations of blood cells carrying somatic mutations expand as the individual ages, and this expansion may elevate risk of blood cancers as well as cardiovascular disease. Individuals at higher risk of CHIP and therefore of CHIP-associated disease can be identified through mutational profiling, and the apparently central role of inflammation in CHIP-associated disease has emerged as a potential therapeutic target. While CHIP is often associated with negative health outcomes, emerging evidence suggests that some CHIP-related mutations may also exert beneficial effects, indicating a more complex role in human health. This review examines current understanding of the epidemiology and clinical significance of CHIP and the role of inflammation in driving its association with disease risk. It explores the mechanisms linking CHIP to inflammation and risk of cardiovascular and other diseases, as well as the potential of personalizing therapies against those diseases for individuals with CHIP.

Keywords: Aging; Atherosclerotic cardiovascular disease; Clinical interventions; Clonal hematopoiesis of indeterminate potential; Inflammation; Somatic mutations.