[Somatic JAK2 gene mutation is an evolving risk factor in cardiovascular diseases]

The JAK/STAT pathway has a central physiological role in the differentiation and effector function of cells of myeloid origin, such as macrophages, neutrophils as well as megakaryocytes, and thus, it contributes to the intensity of the non-specific inflammatory reaction. The pathological activation of the signaling pathway by the V617F variant of the JAK2 gene is a frequent change in myeloproliferative neoplasias serving as a driver mechanism leading to overproliferation of the hemopoetic lineages. However, long-term genetic testing demonstrated the occurrence of JAK2 and other pathogen variants also in the absence of significant clinical changes, a condition called as clonal hemopoesis. The effect of pathogenic JAK2 on cell function, including the inflammatory processes, has been intensively studied also in clonal hemopoesis without manifest myeloproliferative neoplasias. The long-term persistance of the variant V617F could be associated with increased cardiovascular risk, expressed by the high prevalence of ischemic heart disease and aortic atheromatosis. This relation goes back to the molecular pathogenesis of atheroma formation, today principally considered as a complex process of subacute thromboinflammatory events. This hypothesis and the latest findings on JAK2-driven cardiovascular pathology are the subjects of this overview. Orv Hetil. 2024; 165(23): 883–890.