{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:12:32Z","timestamp":1790626352051,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,4,30]],"date-time":"2018-04-30T00:00:00Z","timestamp":1525046400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012538","name":"Swedish Cancer Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012538","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012558","name":"Sk\u00e5ne County Council's Research and Development Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012558","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001424","name":"American Liver Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001424","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003461","name":"Gunnar Nilssons Cancerstiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003461","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006313","name":"Barncancerfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006313","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2018,7]]},"abstract":"Abstract<\/jats:title>Objective<\/jats:title>Philadelphia\u2010negative myeloproliferative neoplasms (MPN<\/jats:styled-content>s) commonly share hyperactive JAK<\/jats:styled-content>\u2010STAT<\/jats:styled-content> signaling affecting hematopoietic stem cells (HSC<\/jats:styled-content>) and their progeny. The JAK<\/jats:styled-content>1\/2 inhibitor Ruxolitinib has remarkable clinical efficacy, including spleen reduction, improvement of constitutional symptoms, and bone marrow (BM<\/jats:styled-content>) fibrosis reversal. Whether this is due to inhibition of JAK<\/jats:styled-content>2\u2010mutated HSC<\/jats:styled-content> only, or whether Ruxolitinib also affects BM<\/jats:styled-content> stroma is not known.<\/jats:p><\/jats:sec>Methods<\/jats:title>This study investigated potential effects of Ruxolitinib on BM<\/jats:styled-content> mesenchymal stromal cells (MSC<\/jats:styled-content>), which are not only major regulators of hematopoiesis but also contribute to fibrosis, from 10 healthy donors and 7 JAK<\/jats:styled-content>2V617F<\/jats:sup>\u2010positive MPN<\/jats:styled-content> patients.<\/jats:p><\/jats:sec>Results<\/jats:title>Ruxolitinib moderately inhibited the growth of healthy donor MSC<\/jats:styled-content> (HD<\/jats:styled-content>\u2010MSC<\/jats:styled-content>) and MSC<\/jats:styled-content> from JAK<\/jats:styled-content>2V617F+<\/jats:sup> MPN<\/jats:styled-content> patients (P\u2010MSC<\/jats:styled-content>) in short\u2010 and long\u2010term assays. The clonogenic potential of HD<\/jats:styled-content>\u2010MSC<\/jats:styled-content> was not affected by Ruxolitinib. JAK<\/jats:styled-content>\u2010STAT<\/jats:styled-content> signaling, however, was markedly inhibited in both HD<\/jats:styled-content>\u2010MSC<\/jats:styled-content> and P\u2010MSC<\/jats:styled-content>, the latter of which showed higher expression of fibrosis\u2010associated and hematopoiesis\u2010maintenance genes. Moreover, Ruxolitinib reduced MSC<\/jats:styled-content> secretion of MCP<\/jats:styled-content>\u20101 and IL<\/jats:styled-content>\u20106.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Ruxolitinib affected JAK<\/jats:styled-content>2 signaling in MSC<\/jats:styled-content> at clinically relevant doses, which is likely to contribute to the normalization of the inflammatory milieu in MPNs<\/jats:styled-content>. Thus, combined HSC<\/jats:styled-content> and stroma\u2010directed interventions have the potential to improve constitutional symptoms and reduce stromal proliferation in MPN<\/jats:styled-content>s.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ejh.13079","type":"journal-article","created":{"date-parts":[[2018,4,12]],"date-time":"2018-04-12T10:10:22Z","timestamp":1523527822000},"page":"57-67","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Effects of JAK<\/scp>1\/2 inhibition on bone marrow stromal cells of myeloproliferative neoplasm (MPN<\/scp>) patients and healthy individuals"],"prefix":"10.1111","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4954-233X","authenticated-orcid":false,"given":"Dimitra","family":"Zacharaki","sequence":"first","affiliation":[{"name":"Division of Molecular Hematology & Lund Stem Cell Center Lund University Lund 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