{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T02:26:47Z","timestamp":1790130407029,"version":"4.0.1"},"reference-count":104,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Clonal hematopoiesis refers to the clonal expansion of hematopoietic stem and progenitor cells, driven by somatic mutations. Major mutated genes in clonal hematopoiesis include genes involved in epigenetic regulation including DNA methylation and\/or chromatin modification (e.g., DNMT3A, TET2, and ASXL1), tumor suppressors (e.g., TP53), signal transduction (e.g., JAK2), and RNA splicing (e.g., SF3B1 and SRSF2). Clonal hematopoiesis includes clonal hematopoiesis of indeterminate potential (CHIP), clonal cytopenia of unknown significance (CCUS), and myelodysplastic syndromes\/neoplasms (MDS). CHIP occurs when the frequency of the variant allele equals or exceeds 2% (4% for X-linked genes in males) in the absence of cytopenias. CHIP is common among older persons and is associated with an increased risk of hematologic cancer. CHIP is also associated with an increased risk of atherosclerotic disease including acute myocardial infarction, stroke, cardiac failure, and abdominal aneurysm. Increasing evidence suggests that CHIP is associated with venous thromboembolic disease. Somatic mutations lead to proliferation of hematopoietic progenitor cells and their progeny, resulting in excessive activation of granulocytes and monocytes. It could be postulated that chronic inflammation caused by clonal expansion of myeloid cells carrying mutations in DNMT3A, TET2, and ASXL1 (\u201cDTA\u201d) genes may constitute an independent risk factor in clot formation and endothelial-cell damage. DTA mutations correlate with elevated proinflammatory cytokines such as IL-1\u03b2 and IL-6 and enhanced activation of inflammasomes. Moreover, JAK2 mutations may have a direct role in the activation of platelets and coagulation. In vivo murine studies have demonstrated that activation of the JAK-STAT signaling pathway promotes neutrophil extracellular trap (NET) formation, contributing to a prothrombotic state. Insights from related clonal disorders such as paroxysmal nocturnal hemoglobinuria and the VEXAS syndrome support the concept that mutation-driven innate immune activation can directly perturb hemostatic balance. This review aims to summarize the association between clonal expansion of hematopoietic cells and thrombotic disease, and highlight how somatic mutations in hematopoietic cells may contribute to vascular disease and thrombogenesis.<\/jats:p>","DOI":"10.3390\/cancers18091326","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T10:38:14Z","timestamp":1776854294000},"page":"1326","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Clonal Hematopoiesis of Indeterminate Potential (CHIP): A Model of Mutation-Driven Thromboinflammation"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-0156-9484","authenticated-orcid":false,"given":"Bouse","family":"Malkots","sequence":"first","affiliation":[{"name":"Department of Hematology, Democritus University of Thrace, 68 100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6458-8201","authenticated-orcid":false,"given":"Iliana","family":"Stamatiou","sequence":"additional","affiliation":[{"name":"Department of Hematology, Democritus University of Thrace, 68 100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuil","family":"Panagiotopoulos","sequence":"additional","affiliation":[{"name":"Department of Hematology, Democritus University of Thrace, 68 100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5302-4511","authenticated-orcid":false,"given":"Lydia","family":"Inglezou","sequence":"additional","affiliation":[{"name":"Department of Hematology, Democritus University of Thrace, 68 100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasiliki","family":"Sakka","sequence":"additional","affiliation":[{"name":"Department of Hematology, Democritus University of Thrace, 68 100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1705-0146","authenticated-orcid":false,"given":"Georgios","family":"Vrachiolias","sequence":"additional","affiliation":[{"name":"Department of Hematology, Democritus University of Thrace, 68 100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7771-7419","authenticated-orcid":false,"given":"Christina","family":"Misidou","sequence":"additional","affiliation":[{"name":"Department of Hematology, Democritus University of Thrace, 68 100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4985-5862","authenticated-orcid":false,"given":"Emmanuil","family":"Spanoudakis","sequence":"additional","affiliation":[{"name":"Department of Hematology, Democritus University of Thrace, 68 100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7668-0186","authenticated-orcid":false,"given":"Ioannis","family":"Kotsianidis","sequence":"additional","affiliation":[{"name":"Department of Hematology, Democritus University of Thrace, 68 100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1165-9639","authenticated-orcid":false,"given":"Konstantinos","family":"Liapis","sequence":"additional","affiliation":[{"name":"Department of Hematology, Democritus University of Thrace, 68 100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1056\/NEJMra1904794","article-title":"Myelodysplastic Syndromes","volume":"383","author":"Cazzola","year":"2020","journal-title":"N. 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