{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T12:16:51Z","timestamp":1784117811123,"version":"3.55.0"},"reference-count":46,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T00:00:00Z","timestamp":1684454400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007427","name":"MPN Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007427","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL134952"],"award-info":[{"award-number":["R01HL134952"]}],"id":[{"id":"10.13039\/100000002","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":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Small molecule inhibitors targeting JAK2 provide symptomatic benefits for myeloproliferative neoplasm (MPN) patients and are among first\u2010line therapeutic agents. However, despite all having potent capacity to suppress JAK\u2013STAT signaling, they demonstrate distinct clinical profiles suggesting contributory effects in targeting other ancillary pathways. Here, we performed comprehensive profiling on four JAK2 inhibitors either FDA\u2010approved (ruxolitinib, fedratinib, and pacritinib) or undergoing phase 3 studies (momelotinib) to better outline mechanistic and therapeutic efficacy. Across <jats:italic>JAK2<\/jats:italic>\u2010mutant in vitro models, all four inhibitors demonstrated similar anti\u2010proliferative phenotypes, whereas pacritinib yielded greatest potency on suppressing colony formation in primary samples, while momelotinib exhibited unique erythroid colony formation sparing. All inhibitors reduced leukemic engraftment, disease burden, and extended survival across patient\u2010derived xenograft (PDX) models, with strongest effects elicited by pacritinib. Through RNA\u2010sequencing and gene set enrichment analyses, differential suppressive degrees of JAK\u2013STAT and inflammatory response signatures were revealed, which we validated with signaling and cytokine suspension mass cytometry across primary samples. Lastly, we assessed the capacity of JAK2 inhibitors to modulate iron regulation, uncovering potent suppression of hepcidin and SMAD signaling by pacritinib. These comparative findings provide insight into the differential and beneficial effects of ancillary targeting beyond JAK2 and may help guide the use of specific inhibitors in personalized therapy.<\/jats:p>","DOI":"10.1002\/ajh.26935","type":"journal-article","created":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T08:20:47Z","timestamp":1684484447000},"page":"1029-1042","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Comprehensive profiling of clinical <scp>JAK<\/scp> inhibitors in myeloproliferative neoplasms"],"prefix":"10.1002","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3240-8989","authenticated-orcid":false,"given":"Tim","family":"Kong","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Medicine Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LaYow","family":"Yu","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo B. 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Department of Medicine Washington University School of Medicine  St. Louis Missouri USA"},{"name":"Immunomonitoring Laboratory, Center for Human Immunology and Immunotherapy Programs Washington University School of Medicine  St. Louis Missouri USA"},{"name":"Department of Pathology and Immunology Washington University School of Medicine  St. Louis Missouri 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