Clonal Hematopoiesis: Confluence of Malignant and Nonmalignant Diseases

Abstract

Clonal hematopoiesis of indeterminate potential (CHIP) is a state in which somatic mutations in hematopoietic stem cells lead to clonal expansion of blood cells in individuals without hematologic malignancy. The mutated genes, including TET2, DNMT3A, ASXL1, TP53, JAK2, and SF3B1, are also recurrently mutated in myeloid malignancies. Individuals with CHIP have an increased risk of developing a hematologic cancer. Moreover, individuals with CHIP have an elevated risk of all-cause mortality that is significantly attributable to cardiovascular disease, independent of traditional risk factors. The mechanism for this increased risk is likely linked to increased inflammation driven by mutated macrophages, in part through inflammasome activation. This has broadened our understanding of how chronic diseases are influenced by CHIP and of the mechanistic role of inflammation in these disorders.