{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T23:24:47Z","timestamp":1774481087394,"version":"3.50.1"},"reference-count":43,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,5,27]],"date-time":"2020-05-27T00:00:00Z","timestamp":1590537600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS104489\u201002 (DWC)"],"award-info":[{"award-number":["R01NS104489\u201002 (DWC)"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01NS055849\u201004 (DWC)"],"award-info":[{"award-number":["U01NS055849\u201004 (DWC)"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50NS052606\u20101 (DWC)"],"award-info":[{"award-number":["P50NS052606\u20101 (DWC)"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Neurofibromatosis type 1 (NF1) is a common genetic disorder characterized by plexiform neurofibromas (pNF), which are thought to be congenital tumors that arise in utero and enlarge throughout life. Genetic studies in murine models delineated an indispensable role for the stem cell factor (SCF)\/c\u2010kit pathway in pNF initiation and progression. A subsequent phase 2 clinical trial using imatinib mesylate to inhibit SCF\/c\u2010kit demonstrated tumor shrinkage in a subset of preexisting pNF; however, imatinib's role on preventing pNF development has yet to be explored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p>We evaluated the effect of imatinib dosed at 10\u2010100\u00a0mg\/kg\/day for 12\u00a0weeks to one\u2010month\u2010old <jats:italic>Nf1<jats:sup>flox\/flox<\/jats:sup>;PostnCre(+)<\/jats:italic> mice, prior to onset of pNF formation. To determine durability of response, we then monitored for pNF growth at later time points, comparing imatinib\u2010 with vehicle\u2010treated mice. We assessed gross and histopathological analysis of tumor burden.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Imatinib administered preventatively led to a significant decrease in pNF number, even at doses as low as 10\u00a0mg\/kg\/day. Tumor development continued to be significantly inhibited after cessation of imatinib dosed at 50 and 100\u00a0mg\/kg\/day. In the cohort of treated mice that underwent prolonged follow\u2010up, the size of residual tumors was significantly reduced as compared with age\u2010matched littermates that received vehicle control.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Early administration of imatinib inhibits pNF genesis in vivo, and effects are sustained after discontinuation of therapy. These findings may guide clinical use of imatinib in young NF1 patients prior to the substantial development of pNF.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.28372","type":"journal-article","created":{"date-parts":[[2020,5,27]],"date-time":"2020-05-27T13:48:53Z","timestamp":1590587333000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Early administration of imatinib mesylate reduces plexiform neurofibroma tumor burden with durable results after drug discontinuation in a mouse model of neurofibromatosis type 1"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7784-0476","authenticated-orcid":false,"given":"Amy E.","family":"Armstrong","sequence":"first","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology Riley Hospital for Children  Indianapolis Indiana"},{"name":"Department of Pediatrics Herman B. 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Wells Center for Pediatric Research  Indianapolis Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Waylan","family":"Bessler","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Herman B. Wells Center for Pediatric Research  Indianapolis Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Ferguson","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology Riley Hospital for Children  Indianapolis Indiana"},{"name":"Department of Pediatrics Herman B. Wells Center for Pediatric Research  Indianapolis Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Herman B. Wells Center for Pediatric Research  Indianapolis Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Herman B. Wells Center for Pediatric Research  Indianapolis Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Herman B. Wells Center for Pediatric Research  Indianapolis Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianlin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Herman B. Wells Center for Pediatric Research  Indianapolis Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng\u2010Chun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Herman B. Wells Center for Pediatric Research  Indianapolis Indiana"},{"name":"Department of Anatomy and Cell Biology Indiana University School of Medicine  Indianapolis Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kent A.","family":"Robertson","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology Riley Hospital for Children  Indianapolis Indiana"},{"name":"Department of Pediatrics Herman B. Wells Center for Pediatric Research  Indianapolis Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Ingram","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Herman B. 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