{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:20:04Z","timestamp":1792120804381,"version":"4.4.0"},"reference-count":38,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2020,8,13]],"date-time":"2020-08-13T00:00:00Z","timestamp":1597276800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["10005"],"award-info":[{"award-number":["10005"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Myeloproliferative neoplasms are divided into essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). Although ruxolitinib was proven to be effective in reducing symptoms, patients rarely achieve complete molecular remission. Therefore, it is relevant to identify new therapeutic targets to improve the clinical outcome of patients. Bcl\u2010xL protein, the long isoform encoded by alternative splicing of the <jats:italic>Bcl\u2010x<\/jats:italic> gene, acts as an anti\u2010apoptotic regulator. Our study investigated the role of Bcl\u2010xL as a marker of severity of MPN and the possibility to target Bcl\u2010xL in patients. 129 MPN patients and 21 healthy patients were enrolled in the study. We analysed <jats:italic>Bcl\u2010xL<\/jats:italic> expression in leucocytes and in enriched CD34+ and CD235a+ cells. Furthermore, ABT\u2010737, a Bcl\u2010xL inhibitor, was tested in HEL cells and in leucocytes from MPN patients. Bcl\u2010xL was found progressively over\u2010expressed in cells from ET, PV and PMF patients, independently by JAK2 mutational status. Moreover, our data indicated that the combination of ABT\u2010737 and ruxolitinib resulted in a significantly higher apoptotic rate than the individual drug. Our study suggests that Bcl\u2010xL plays an important role in MPN independently from JAK2 V617F mutation. Furthermore, data demonstrate that targeting simultaneously JAK2 and Bcl\u2010xL might represent an interesting new approach.<\/jats:p>","DOI":"10.1111\/jcmm.15730","type":"journal-article","created":{"date-parts":[[2020,8,13]],"date-time":"2020-08-13T13:40:45Z","timestamp":1597326045000},"page":"10978-10986","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Bcl\u2010xL represents a therapeutic target in Philadelphia negative myeloproliferative neoplasms"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8640-2462","authenticated-orcid":false,"given":"Jessica","family":"Petiti","sequence":"first","affiliation":[{"name":"Department of Clinical and Biological Sciences University of Turin Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Lo Iacono","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences University of Turin Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Rosso","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences University of Turin Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Andreani","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences University of Turin Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandar","family":"Jovanovski","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences University of Turin Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Podest\u00e0","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hemato\u2010Oncology and Stem Cell and Cellular Therapy Laboratory Institute G. 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