{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T15:09:10Z","timestamp":1793372950988,"version":"4.5.0"},"reference-count":107,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T00:00:00Z","timestamp":1697500800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>In this article, we reviewed the possible mechanisms linking the clonal hematopoiesis of indeterminate potential (CHIP) to chronic myeloproliferative neoplasms (MPNs), autoimmune diseases (ADs), and cardiovascular diseases (CADs). CHIP is characterized by the presence of clonal mutations with an allelic frequency &amp;gt;2% in the peripheral blood without dysplasia, overt hematological neoplasms, or abnormalities in blood cell count. The prevalence may reach 20% of elderly healthy individuals and is considered a risk factor for myelodysplastic neoplasms and acute leukemia. In MPNs, CHIP is often associated with mutations such as <jats:italic>JAK2V617F<\/jats:italic> or <jats:italic>DNMT3A, TET2<\/jats:italic>, or <jats:italic>ASXL1<\/jats:italic>, which exhibit a 12.1- and 1.7\u20132-fold increase in CADs. Specifically, <jats:italic>JAK2<\/jats:italic>-mutated cells produce excessive cytokines and reactive oxygen species, leading to proinflammatory modifications in the bone marrow microenvironment. Consequently, the likelihood of experiencing thrombosis is influenced by the variant allele frequency (VAF) of the <jats:italic>JAK2V617F<\/jats:italic> mutation, which also appears to be correlated with anti-endothelial cell antibodies that sustain thrombosis. However, <jats:italic>DNMT3A<\/jats:italic> mutations induce pro-inflammatory T-cell polarization and activate the inflammasome complex, while <jats:italic>TET2<\/jats:italic> downregulation leads to endothelial cell autophagy and inflammatory factor upregulation. As a result, in patients with <jats:italic>TET2<\/jats:italic> and <jats:italic>DNMT3A-<\/jats:italic>related CHIP, the inflammasome hyperactivation represents a potential cause of CADs. CHIP also occurs in patients with large and small vessel vasculitis, while ADs are more frequently associated with MPNs. In these diseases, monocytes and neutrophils play a key role in the formation of neutrophil extracellular trap (NET) as well as anti-endothelial cell antibodies, resulting in a final procoagulant effect. ADs, such as systemic lupus erythematosus, psoriasis, and arthritis, are also characterized by an overexpression of the Rho-associated coiled-coil containing protein kinase 2 (ROCK2), a serine\/threonine kinase that can hyperactivate the JAK-STAT pathway. Interestingly, hyperactivation of <jats:italic>ROCK2<\/jats:italic> has also been observed in myeloid malignancies, where it promotes the growth and survival of leukemic cells. In summary, the presence of CHIP, with or without neoplasia, can be associated with autoimmune manifestations and thrombosis. In the presence of these manifestations, it is necessary to consider a \u201cdisease-modifying therapy\u201d that may either reduce the clonal burden or inhibit the clonally activated JAK pathway.<\/jats:p>","DOI":"10.3389\/fmed.2023.1254868","type":"journal-article","created":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T08:45:55Z","timestamp":1697532355000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Philadelphia chromosome-negative myeloproliferative chronic neoplasms: is clonal hematopoiesis the main determinant of autoimmune and cardio-vascular 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