Clonal hematopoiesis of unknown potential and cardiovascular disease – literature review

Somatic mutations in hematopoietic stem cells (HSCs) are an inevitable part of human aging. When these mutations reach a certain variant allele frequency (VAF), they may confer a proliferative advantage to mutated clones, leading to clonal hematopoiesis. Once the HSCs generate over 10¹⁰-10¹² mutated cells, they can initiate various myeloid or lymphoid malignancies. In cases where the VAF exceeds 2% (roughly 10⁴ mutated blood cells) but without clinical evidence of hematologic cancer, the condition is termed clonal hematopoiesis of indeterminate potential (CHIP). Numerous studies have identifi ed that CHIP is frequently driven by mutations in genes implicated in hematologic malignancies, most notably TET2 , DNMT3A , and JAK2 . CHIP has also been strongly linked to cardiovascular diseases, particularly atherosclerosis. This dual role highlights a shared pathogenesis between cardiovascular and hematologic disorders through mutations in HSCs. CHIP-associated monocytes exhibit a pro-infl ammatory phenotype, activating infl ammasomes and overexpressing cytokines such as interleukin (IL)-1β and IL-6, as well as chemokines like Cxcl1-3 and Pf4. This leads to a chronic infl ammatory loop that contributes to endothelial dysfunction and atherosclerosis. Current data suggest that CHIP poses a cardiovascular risk comparable to traditional risk factors. Ongoing research continues to uncover the complex mechanisms underlying this association.