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Lykfeldt og Hustrus Legat","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009906","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004331","name":"Snedkermester Sophus Jacobsen og Hustru Astrid Jacobsens Fond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004331","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The <jats:italic>JAK2V617F<\/jats:italic> mutation is associated with increased cardiovascular risk, including ischaemic stroke. This study investigates the prevalence of additional mutations in ischaemic cerebrovascular patients with and without <jats:italic>JAK2V617F<\/jats:italic> to better understand the mechanisms contributing to thrombotic risk. We examined 63 patients with the <jats:italic>JAK2V617F<\/jats:italic> mutation and 126 matched controls from a cohort of 591 ischaemic cerebrovascular patients. Somatic mutations were assessed using targeted next\u2010generation sequencing (NGS). Serum thromboinflammatory markers were evaluated in a subset of patients. Additional somatic mutations were more common in <jats:italic>JAK2V617F<\/jats:italic>\u2010positive patients than in controls (47.6% vs. 30.2%, <jats:italic>p<\/jats:italic>\u2009=\u20090.028). Patients with <jats:italic>JAK2V617F<\/jats:italic> had a higher prevalence of other mutations with variant allele frequencies (VAFs) above 10% (23.8% vs. 7.9%, <jats:italic>p<\/jats:italic>\u2009=\u20090.005), a pattern that persisted in cases with <jats:italic>JAK2V617F<\/jats:italic> &lt;1% (<jats:italic>p<\/jats:italic>\u2009=\u20090.019). In <jats:italic>JAK2V617F<\/jats:italic>\u2010positive patients, additional somatic mutations were associated with higher monocyte levels, even when excluding myeloproliferative neoplasms patients (<jats:italic>p<\/jats:italic>\u2009=\u20090.011). Patients with other clonal haematopoiesis of indeterminate potential mutations exhibited higher vascular cell adhesion molecule 1 (<jats:italic>p<\/jats:italic>\u2009=\u20090.027), soluble urokinase plasminogen activator receptor (<jats:italic>p<\/jats:italic>\u2009=\u20090.010) and IL\u201010 (<jats:italic>p<\/jats:italic>\u2009=\u20090.045), as well as higher neutrophil to lymphocyte ratio (<jats:italic>p<\/jats:italic>\u2009=\u20090.002). Ischaemic cerebrovascular patients with the <jats:italic>JAK2V617F<\/jats:italic> mutation more frequently harbour other somatic mutations and at higher VAF. This may reflect a more advanced clonal profile with relevance for vascular risk in <jats:italic>JAK2V617F<\/jats:italic>\u2010positive individuals.<\/jats:p>","DOI":"10.1111\/bjh.20242","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T01:53:32Z","timestamp":1753322012000},"page":"1029-1037","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Prevalence and impact of additional <scp>CHIP<\/scp> mutations in <i>JAK2V617F<\/i>\u2010positive ischaemic cerebrovascular patients"],"prefix":"10.1111","volume":"207","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4285-6766","authenticated-orcid":false,"given":"Marie Hvelplund","family":"Kristiansen","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"},{"name":"Department of Neurology Zealand University Hospital  Roskilde 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Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus Henrik","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Section for Oral Biology and Immunopathology, Department of Odontology, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"},{"name":"Institute for Inflammation Research, Center for Rheumatology and Spine Diseases Copenhagen University Hospital Rigshospitalet  Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3936-8032","authenticated-orcid":false,"given":"Hans Carl","family":"Hasselbalch","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"},{"name":"Department of Hematology Zealand University Hospital  Roskilde 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