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In this regard, the impact of <jats:italic>JAK2<\/jats:italic>V617F variant allele frequency (VAF) is still debated. The purpose of the current study was to analyze the impact of <jats:italic>JAK2<\/jats:italic>V617F VAF in the context of other established risk factors for thrombosis in a total of 865 2016 WHO-defined PV patients utilizing two independent cohorts: University of Florence (<jats:italic>n<\/jats:italic>\u2009=\u2009576) as a training cohort and Policlinico Gemelli, Catholic University, Rome (<jats:italic>n<\/jats:italic>\u2009=\u2009289) as a validation cohort. In the training cohort VT free-survival was significantly shorter in the presence of a <jats:italic>JAK2<\/jats:italic>V617F VAF\u2009&gt;\u200950% (HR 4; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), whereas no difference was found for AT (HR 0.9; <jats:italic>p<\/jats:italic>\u2009=\u20090.8). Multivariable analysis identified <jats:italic>JAK2<\/jats:italic>V617F VAF\u2009&gt;\u200950% (HR 3.8, <jats:italic>p<\/jats:italic>\u2009=\u20090.001) and previous VT (HR 2.2; <jats:italic>p<\/jats:italic>\u2009=\u20090.04) as independent risk factors for future VT whereas diabetes (HR 2.4; <jats:italic>p<\/jats:italic>\u2009=\u20090.02), hyperlipidemia (HR 2.3; <jats:italic>p<\/jats:italic>\u2009=\u20090.01) and previous AT (HR 2; <jats:italic>p<\/jats:italic>\u2009=\u20090.04) were independent risk factors for future AT. Similarly, <jats:italic>JAK2<\/jats:italic>V617F VAF\u2009&gt;\u200950% (HR 2.4; <jats:italic>p<\/jats:italic>\u2009=\u20090.01) and previous VT (HR 2.8; <jats:italic>p<\/jats:italic>\u2009=\u20090.005) were confirmed as independent predictors of future VT in the validation cohort. Impact of <jats:italic>JAK2<\/jats:italic>V617F VAF\u2009&gt;\u200950% on VT was particularly significant in conventional low-risk patients, both in Florence (HR 10.6, <jats:italic>p<\/jats:italic>\u2009=\u20090.005) and Rome cohort (HR 4; <jats:italic>p<\/jats:italic>\u2009=\u20090.02). In conclusion, we identified <jats:italic>JAK2<\/jats:italic>V617F VAF\u2009&gt;\u200950% as an independent strong predictor of VT, supporting that AT and VT are different entities which might require distinct management.<\/jats:p>","DOI":"10.1038\/s41408-021-00581-6","type":"journal-article","created":{"date-parts":[[2021,12,11]],"date-time":"2021-12-11T15:02:42Z","timestamp":1639234962000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":116,"title":["JAK2V617F variant allele frequency &gt;50% identifies patients with polycythemia vera at high risk for venous thrombosis"],"prefix":"10.1038","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1809-284X","authenticated-orcid":false,"given":"Paola","family":"Guglielmelli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6241-1206","authenticated-orcid":false,"given":"Giuseppe G.","family":"Loscocco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmela","family":"Mannarelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4810-6501","authenticated-orcid":false,"given":"Francesco","family":"Mannelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Ramundo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Coltro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Betti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Maccari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Ceglie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1355-1587","authenticated-orcid":false,"given":"Patrizia","family":"Chiusolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Paoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2747-6327","authenticated-orcid":false,"given":"Tiziano","family":"Barbui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4605-3821","authenticated-orcid":false,"given":"Ayalew","family":"Tefferi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5178-5827","authenticated-orcid":false,"given":"Valerio","family":"De Stefano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5755-0730","authenticated-orcid":false,"given":"Alessandro M.","family":"Vannucchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,12,11]]},"reference":[{"key":"581_CR1","doi-asserted-by":"crossref","unstructured":"Loscocco GG, Guglielmelli P, Vannucchi AM. 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VDS received personal fees for advisory board and\/or lectures from AbbVie, AOP Orphan Pharmaceutical, and Novartis, and research grants from AbbVie and Novartis. AMV received personal fees for advisory board and\/or lectures from Novartis, AbbVie, AOP Pharmaceuticals, BMS and Incyte. All other authors have no conflict to report.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"199"}}