{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T06:13:42Z","timestamp":1789193622761,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    Myelofibrosis (MF) is a chronic myeloproliferative neoplasm (MPN) characterized by splenomegaly, constitutional symptoms, marrow fibrosis, cytopenias and inflammation. Janus kinase 2 (JAK2) inhibitors, such as ruxolitinib, reduce splenomegaly and alleviate symptoms but have limited disease\u2010modifying activity, and resistance frequently develops. Selinexor, an oral selective exportin (XPO1) inhibitor, restores nuclear retention of tumour suppressors and inhibitors of inflammatory signalling. Dual XPO1\/JAK2 inhibition targets complementary downstream pathways, enhancing suppression of MF progenitor cell fitness. We evaluated selinexor plus ruxolitinib in MF models, including\n                    <jats:italic>JAK2<\/jats:italic>\n                    V617F or calreticulin (\n                    <jats:italic>CALR<\/jats:italic>\n                    ) exon 9\u2010mutant MPN cell lines and samples from patients with MF. The combination showed greater anti\u2010proliferative activity than JAK2 inhibition alone and suppressed colony formation from MF Cluster of Differentiation 34 (CD34)+ cells. Selinexor remained active in a ruxolitinib\u2010resistant MPN cell line, inducing G1 arrest and apoptosis. Multi\u2010omic analyses demonstrated increased nuclear retention of p53 and disruption of Nuclear factor kappa\u2010light\u2010chain\u2010enhancer of activated B cells (NF\u2010\u03baB) and Janus Kinase\/Signal Transducer and Activator of Transcription (JAK\/STAT) signalling, complementing and extending ruxolitinib\u2010targeted pathways. The combination suppressed NF\u2010\u03baB transcriptional activity and reduced Tumor Necrosis Factor alpha (TNF\u03b1), Interleukin\u20106 (IL\u20106) and Monocyte Chemoattractant Protein\u20101 (MCP\u20101) secretion from MF patient peripheral blood mononuclear cells. These findings highlight that selinexor plus ruxolitinib affects both MF haematopoietic cell\u2013intrinsic and microenvironment\u2010related pathways, providing a novel disease\u2010modifying strategy with the potential to improve clinical outcomes in patients with MF.\n                  <\/jats:p>","DOI":"10.1111\/bjh.70639","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T23:57:27Z","timestamp":1784073447000},"page":"988-997","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting nuclear export and Janus Kinase\/Signal Transducer and Activator of Transcription (\n                    <scp>JAK<\/scp>\n                    \/\n                    <scp>STAT)<\/scp>\n                    signalling in myelofibrosis: A novel combinatorial strategy that impacts intrinsic and microenvironment\u2010related pathways"],"prefix":"10.1111","volume":"209","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8784-5641","authenticated-orcid":false,"given":"Trinayan","family":"Kashyap","sequence":"first","affiliation":[{"name":"Karyopharm Therapeutics  Newton Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea A.","family":"Ellero","sequence":"additional","affiliation":[{"name":"Karyopharm Therapeutics  Newton Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Walker","sequence":"additional","affiliation":[{"name":"Karyopharm Therapeutics  Newton Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie E.","family":"Maloof","sequence":"additional","affiliation":[{"name":"Karyopharm Therapeutics  Newton Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Lu","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology Section, Tisch Cancer Institute and Department of Medicine, Myeloproliferative Neoplasm\u2010Research Consortium Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Xia","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology Section, Tisch Cancer Institute and Department of Medicine, Myeloproliferative Neoplasm\u2010Research Consortium Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology Section, Tisch Cancer Institute and Department of Medicine, Myeloproliferative Neoplasm\u2010Research Consortium Icahn School of Medicine at Mount Sinai  New York New York 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