{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T02:55:44Z","timestamp":1788317744499,"version":"build-2803163510"},"reference-count":60,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,6,6]],"date-time":"2024-06-06T00:00:00Z","timestamp":1717632000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021856","name":"MUR","doi-asserted-by":"publisher","award":["2022F4WMR3"],"award-info":[{"award-number":["2022F4WMR3"]}],"id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["NET\u20102018\u201012365935"],"award-info":[{"award-number":["NET\u20102018\u201012365935"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The variant allele frequency (VAF) of driver mutations (\n                    <jats:italic>JAK2, CALR<\/jats:italic>\n                    ) in myeloproliferative neoplasms is associated with features of advanced disease and complications. Ruxolitinib and interferon were reported to variably reduce the mutant VAF, but the long\u2010term impact of molecular responses (MR) remains debated. We prospectively measured changes in\n                    <jats:italic>JAK2<\/jats:italic>\n                    and\n                    <jats:italic>CALR<\/jats:italic>\n                    VAF in 77 patients with polycythemia vera and essential thrombocythemia, treated with ruxolitinib for a median of 8\u2009years, and assessed correlation with complete clinical and hematological response (CCHR) and outcomes. At last observation time,\n                    <jats:italic>JAK2<\/jats:italic>\n                    VAF reduced overall from a median of 68% (range, 20%\u201399%) to 3.5% (0%\u201398%). A profound and durable MR (DMR; defined as a VAF stably \u22642%), including complete MR in 8%, was achieved in 20% of the patients, a partial MR (PMR; VAF reduction &gt;50% of the baseline level) in 25%, and 56% had no molecular response (NMR). A CCHR was reached by 69% overall, independently of any degree of MR achieved; conversely, a DMR correlated with longer duration of CCHR and, most importantly, with reduced rate of progression to myelofibrosis and with longer myelofibrosis\u2010free, event\u2010free and progression\u2010free survival. Achievement of PMR also had some favorable impact on outcomes, compared to NMR. A baseline\n                    <jats:italic>JAK2<\/jats:italic>\n                    VAF &lt;50%, and a VAF reduction of \u226535% after 2\u2009years of treatment, predicted for the achievement of DMR and reduced progression to myelofibrosis. Overall, these findings support the clinical value of achieving profound, durable MR and its consideration as surrogate endpoint in future clinical trials.\n                  <\/jats:p>","DOI":"10.1002\/ajh.27400","type":"journal-article","created":{"date-parts":[[2024,6,6]],"date-time":"2024-06-06T05:23:33Z","timestamp":1717651413000},"page":"1550-1559","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Clinical impact of mutated\n                    <scp>JAK2<\/scp>\n                    allele burden reduction in polycythemia vera and essential thrombocythemia"],"prefix":"10.1002","volume":"99","author":[{"given":"Paola","family":"Guglielmelli","sequence":"first","affiliation":[{"name":"CRIMM, Center Research and Innovation of Myeloproliferative Neoplasms, DMSC, University of Florence, AOU Careggi  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Mora","sequence":"additional","affiliation":[{"name":"S.C. 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