{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:55:44Z","timestamp":1791114944282,"version":"4.1.0"},"reference-count":37,"publisher":"American Society of Hematology","issue":"5","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,9,1]]},"abstract":"<jats:p>To prevent the development of acute graft-versus-host disease (GVHD) in lethally irradiated C57BL\/6 (H-2b) recipient mice transplanted with bone marrow\u2013splenocyte grafts from major histocompatibility complex (MHC) disparate BALB\/c mice (H-2d), recipient mice were treated with the rationally designed JAK3 inhibitor WHI-P131 [4-(4\u2032-hydroxyphenyl)-amino-6,7-dimethoxyquinazoline] (20 mg\/kg, 3 times a day [tid]) daily from the day of bone marrow transplantation (BMT) until the end of the 85-day observation period. Total body irradiation (TBI)-conditioned, vehicle-treated control C57BL\/6 mice (n\u2009=\u200938) receiving bone marrow\u2013splenocyte grafts from BALB\/c mice survived acute TBI toxicity, but they all developed histologically confirmed severe multi-organ GVHD and died after a median survival time of 37 days. WHI-P131 treatment (20 mg\/kg intraperitoneally, tid) prolonged the median survival time of the BMT recipients to 56 days. The probability of survival at 2 months after BMT was 11%\u2009\u00b1\u20095% for vehicle-treated control mice (n\u2009=\u200938) and 41%\u2009\u00b1\u20099% for mice treated with WHI-P131 (n\u2009=\u200932) (P\u2009&amp;lt;\u2009.0001). Notably, the combination regimen WHI-P131 plus the standard anti-GVHD drug methotrexate (MTX) (10 mg\/m2 per day) was more effective than WHI-P131 or MTX alone. More than half the C57BL\/6 recipients receiving this most effective GVHD prophylaxis remained alive and healthy throughout the 85-day observation period, with a cumulative survival probability of 70%\u2009\u00b1\u200910%. Taken together, these results indicate that targeting JAK3 in alloreactive donor lymphocytes with a chemical inhibitor such as WHI-P131 may attenuate the severity of GVHD after BMT.<\/jats:p>","DOI":"10.1182\/blood.v98.5.1607","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T12:46:47Z","timestamp":1027774007000},"page":"1607-1613","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":51,"title":["Targeting Janus kinase 3 to attenuate the severity of acute graft-versus-host disease across the major histocompatibility barrier in mice"],"prefix":"10.1182","volume":"98","author":[{"given":"Marina","family":"Cetkovic-Cvrlje","sequence":"first","affiliation":[{"name":"From the Experimental BMT Program, Parker Hughes Cancer Center, and the Departments of Immunology, Pathology, Chemistry, and Drug Discovery Program, Parker Hughes Institute, St Paul, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertram A.","family":"Roers","sequence":"additional","affiliation":[{"name":"From the Experimental BMT Program, Parker Hughes Cancer Center, and the Departments of Immunology, Pathology, Chemistry, and Drug Discovery Program, Parker Hughes Institute, St Paul, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Waurzyniak","sequence":"additional","affiliation":[{"name":"From the Experimental BMT Program, Parker Hughes Cancer Center, and the Departments of Immunology, Pathology, Chemistry, and Drug Discovery Program, Parker Hughes Institute, St Paul, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing-Ping","family":"Liu","sequence":"additional","affiliation":[{"name":"From the Experimental BMT Program, Parker Hughes Cancer Center, and the Departments of Immunology, Pathology, Chemistry, and Drug Discovery Program, Parker Hughes Institute, St Paul, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatih M.","family":"Uckun","sequence":"additional","affiliation":[{"name":"From the Experimental BMT Program, Parker Hughes Cancer Center, and the Departments of Immunology, Pathology, Chemistry, and Drug Discovery Program, Parker Hughes Institute, St Paul, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2020021221534267400_B1","volume-title":"Allogeneic Transplantation.","author":"O'Reilly","year":"1997"},{"key":"2020021221534267400_B2","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1097\/00001622-199503000-00004","article-title":"Mismatched bone marrow transplantation.","volume":"7","author":"Henslee-Downey","year":"1995","journal-title":"Curr Opin Oncol."},{"key":"2020021221534267400_B3","first-page":"401","article-title":"Graft-versus-host disease prophylaxis for matched unrelated donor bone marrow transplantation: comparison between 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