{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T06:23:13Z","timestamp":1791181393787,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,5,23]],"date-time":"2013-05-23T00:00:00Z","timestamp":1369267200000},"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":["Br J Haematol"],"published-print":{"date-parts":[[2013,8]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Myelofibrosis (<jats:styled-content style=\"fixed-case\">MF<\/jats:styled-content>) is a <jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>hiladelphia chromosome\u2013negative stem cell myeloproliferative neoplasm (<jats:styled-content style=\"fixed-case\">MPN<\/jats:styled-content>) associated with cytopenias, splenomegaly, constitutional symptoms, and poor prognosis. <jats:styled-content style=\"fixed-case\">MF<\/jats:styled-content> patients commonly express <jats:italic><jats:styled-content style=\"fixed-case\">JAK<\/jats:styled-content>2 <\/jats:italic><jats:styled-content style=\"fixed-case\">V<\/jats:styled-content>617<jats:styled-content style=\"fixed-case\">F<\/jats:styled-content> mutation and activation of <jats:styled-content style=\"fixed-case\">J<\/jats:styled-content>anus kinase (<jats:styled-content style=\"fixed-case\">JAK<\/jats:styled-content>)\/signal transducer and activator of transcription (<jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>) signalling. Agents targeting the <jats:styled-content style=\"fixed-case\">JAK<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content> pathway have demonstrated efficacy in patients with <jats:styled-content style=\"fixed-case\">MF<\/jats:styled-content>. This study evaluated panobinostat, a pan\u2010deacetylase inhibitor that depletes <jats:styled-content style=\"fixed-case\">JAK<\/jats:styled-content>2 <jats:styled-content style=\"fixed-case\">V<\/jats:styled-content>617<jats:styled-content style=\"fixed-case\">F<\/jats:styled-content> levels and <jats:styled-content style=\"fixed-case\">JAK<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content> signalling in <jats:styled-content style=\"fixed-case\">MPN<\/jats:styled-content> cells, in patients with primary <jats:styled-content style=\"fixed-case\">MF<\/jats:styled-content>, post\u2013essential thrombocythaemia <jats:styled-content style=\"fixed-case\">MF<\/jats:styled-content>, and post\u2013polycythaemia vera <jats:styled-content style=\"fixed-case\">MF<\/jats:styled-content>. Patients received panobinostat 40\u00a0mg administered three times per week. Dose reductions were permitted for toxicities. The primary endpoint was response rate at 6\u00a0months using <jats:styled-content style=\"fixed-case\">I<\/jats:styled-content>nternational <jats:styled-content style=\"fixed-case\">W<\/jats:styled-content>orking <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>roup for <jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>yelofibrosis <jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>esearch and <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>reatment (<jats:styled-content style=\"fixed-case\">IWG<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MRT<\/jats:styled-content>) consensus criteria. Analyses of peripheral blood cells from treated patients revealed that panobinostat inhibited <jats:styled-content style=\"fixed-case\">JAK<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content> signalling, decreased inflammatory cytokine levels, and decreased <jats:italic><jats:styled-content style=\"fixed-case\">JAK<\/jats:styled-content>2 <\/jats:italic><jats:styled-content style=\"fixed-case\">V<\/jats:styled-content>617<jats:styled-content style=\"fixed-case\">F<\/jats:styled-content> allelic burden. However, panobinostat was poorly tolerated at the dose and schedule evaluated, and only 16 of 35 patients completed \u22652 cycles of treatment. One patient (3%) achieved an <jats:styled-content style=\"fixed-case\">IWG<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MRT<\/jats:styled-content> response. Common adverse events were thrombocytopenia (71\u00b74%) and diarrhoea (80\u00b70%). Although molecular correlative analyses suggested that panobinostat inhibits key intracellular targets, limited clinical activity was observed because of poor tolerance.<\/jats:p>","DOI":"10.1111\/bjh.12384","type":"journal-article","created":{"date-parts":[[2013,5,23]],"date-time":"2013-05-23T13:20:47Z","timestamp":1369315247000},"page":"326-335","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Phase <scp>II<\/scp> trial of panobinostat, an oral pan\u2010deacetylase inhibitor in patients with primary myelofibrosis, post\u2013essential thrombocythaemia, and post\u2013polycythaemia vera myelofibrosis"],"prefix":"10.1111","volume":"162","author":[{"given":"Daniel J.","family":"DeAngelo","sequence":"first","affiliation":[{"name":"Dana\u2010Farber Cancer Institute Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruben 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