TET2-CHIP: From Mutation to Malady

Somatic mutations in hematopoietic cells can drive clonal expansion without overt malignancy, a condition defined as clonal hematopoiesis of intermediate potential (CHIP). Among CHIP driver genes, TET2 is notable for its high prevalence and strong association with cardiovascular disease (CVD) and chronic inflammation. TET2 encodes a methylcytosine dioxygenase essential for epigenetic regulation, and its loss impairs hematopoietic stem cell differentiation while altering the functions of mature myeloid and lymphoid cells. Aging-related inflammation, along with lifestyle exposures, metabolic disorders, cancer therapy, and HIV infection, affects the emergence and expansion of TET2-mutant clones. Recently, evidence increasingly links TET2-CHIP to the incidence and prognosis of diverse CVDs. Emerging studies also suggest potential therapeutic strategies for TET2-CHIP-associated cardiovascular disease. This review summarizes current understanding of TET2 biology, mechanisms of TET2-CHIP development, and its cardiovascular implications.