{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:38:58Z","timestamp":1788914338850,"version":"build-2803163510"},"reference-count":29,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T00:00:00Z","timestamp":1747267200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Polycythemia vera (PV) is invariably associated with a <jats:italic>JAK2<\/jats:italic> mutation, with over 50% of patients harboring additional non\u2010<jats:italic>JAK2<\/jats:italic> mutations. In the current study, 319 patients with PV underwent NGS at diagnosis or in chronic phase PV (Group A: <jats:italic>N<\/jats:italic>\u2009=\u2009270, 85%) or at the time of fibrotic (Group B; <jats:italic>N<\/jats:italic>\u2009=\u200937, 12%) or leukemic (Group C; <jats:italic>N<\/jats:italic>\u2009=\u200912, 4%) transformation. Mutational frequencies involving <jats:italic>TP53\/SRSF2\/IDH1\/U2AF1<\/jats:italic> were significantly (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) different between patients in the mutually exclusive Groups A (2%\/4%\/2%\/0.4%), B (8%\/0%\/0%\/5%), and C (50%\/25%\/17%\/8%). Analyses on phenotype\/genotype associations and prognostic impact on overall (OS), leukemia\u2010free (LFS), and myelofibrosis\u2010free (MFFS) survival were limited to Group A patients. <jats:italic>ASXL1<\/jats:italic><jats:sup>MUT<\/jats:sup> was associated with younger age (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01), <jats:italic>SRSF2<\/jats:italic><jats:sup>MUT<\/jats:sup> with older age and leukocytosis (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01), and <jats:italic>TP53<\/jats:italic><jats:sup>MUT<\/jats:sup> with leukocytosis (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01). Mutation co\u2010segregation was apparent between <jats:italic>ASXL1<\/jats:italic> and <jats:italic>IDH2<\/jats:italic> (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01) or <jats:italic>SRSF2<\/jats:italic> (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01), <jats:italic>SRSF2<\/jats:italic> and <jats:italic>IDH2<\/jats:italic> (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01), and <jats:italic>TP53<\/jats:italic> and <jats:italic>NRAS<\/jats:italic> (<jats:italic>p<\/jats:italic>\u2009=\u20090.01). Multivariable analysis identified <jats:italic>SRSF2<\/jats:italic><jats:sup>MUT<\/jats:sup> (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01; HR, 4.2, 1.9\u20139.5), <jats:italic>IDH2<\/jats:italic><jats:sup>MUT<\/jats:sup> (<jats:italic>p<\/jats:italic>\u2009=\u20090.01; HR, 5.3, 1.8\u201315.3), <jats:italic>ASXL1<\/jats:italic><jats:sup>MUT<\/jats:sup> (<jats:italic>p<\/jats:italic>\u2009=\u20090.04; HR, 2.0, 1.1\u20133.7), leukocyte count \u2265\u200915\u2009\u00d7\u200910<jats:sup>9<\/jats:sup>\/L (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01; HR 2.0, 1.3\u20133.1), and advanced age (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01) as risk factors for OS. Median OS in the presence (<jats:italic>N<\/jats:italic>\u2009=\u2009235; 87%) or absence (<jats:italic>N<\/jats:italic>\u2009=\u200935; 13%) of any adverse mutation (i.e., <jats:italic>SRSF2<\/jats:italic><jats:sup>MUT<\/jats:sup>, <jats:italic>ASXL1<\/jats:italic><jats:sup>MUT<\/jats:sup>, or <jats:italic>IDH2<\/jats:italic><jats:sup>MUT<\/jats:sup>) was 8.8 versus 17.8\u2009years (<jats:italic>p<\/jats:italic>\u2009=\u20090.01; HR 1.8, 1.1\u20132.9). In addition, <jats:italic>ASXL1<\/jats:italic><jats:sup>MUT<\/jats:sup> (<jats:italic>p<\/jats:italic>\u2009=\u20090.02; HR, 1.6\u201324.9), <jats:italic>SRSF2<\/jats:italic><jats:sup>MUT<\/jats:sup> (<jats:italic>p<\/jats:italic>\u2009=\u20090.06; HR, 11.9, 1.1\u2013126.2), and advanced age (<jats:italic>p<\/jats:italic>\u2009=\u20090.04) were associated with inferior LFS, and <jats:italic>SRSF2<\/jats:italic><jats:sup>MUT<\/jats:sup> (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01; HR, 24.0, 5.5\u2013103.8) and abnormal karyotype (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01; HR 3.8, 1.6\u20138.9) with inferior MFFS. The number of non\u2010<jats:italic>JAK2<\/jats:italic> mutations was significant in predicting outcome in univariate but not multivariable analysis. The observations from the current study highlight the prognostic significance of non\u2010<jats:italic>JAK2<\/jats:italic> mutations in PV and the prospect of their inclusion in future prognostic models.<\/jats:p>","DOI":"10.1002\/ajh.27717","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T08:49:56Z","timestamp":1747298996000},"page":"1343-1353","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Mutational Landscape in Polycythemia Vera: Phenotype, Genotype, and Prognostic Correlates"],"prefix":"10.1002","volume":"100","author":[{"given":"Masooma S.","family":"Rana","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Medicine Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moazah","family":"Iftikhar","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine 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