{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T04:13:54Z","timestamp":1788236034871,"version":"build-2803163510"},"reference-count":20,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2018,5,16]],"date-time":"2018-05-16T00:00:00Z","timestamp":1526428800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Sharon D. Lund Foundation"},{"DOI":"10.13039\/100007899","name":"University of Arizona","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007899","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Phoenix Children's Hospital Foundation"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Patients with Langerhans cell histiocytosis (LCH) harbor BRAF V600E and activating mutations of <jats:italic>MAP2K1\/MEK1<\/jats:italic> in 50% and 25% of cases, respectively. We evaluated a patient with treatment\u2010refractory LCH for mutations in the RAS\u2010RAF\u2010MEK\u2010ERK pathway and identified a novel mutation in the <jats:italic>MAP2K1<\/jats:italic> gene resulting in a p.L98_K104\u00a0&gt;\u00a0Q deletion and predicted to be auto\u2010activating. During treatment with the MEK inhibitor trametinib, the patient's disease showed significant progression. <jats:italic>In vitro<\/jats:italic> characterization of the MAP2K1 p.L98_K104\u00a0&gt;\u00a0Q deletion confirmed its effect on cellular activation of the ERK pathway and drug resistance.<\/jats:p>","DOI":"10.1002\/pbc.27237","type":"journal-article","created":{"date-parts":[[2018,5,16]],"date-time":"2018-05-16T18:40:34Z","timestamp":1526496034000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Clinical resistance associated with a novel <i>MAP2K1<\/i> mutation in a patient with Langerhans cell histiocytosis"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7747-8457","authenticated-orcid":false,"given":"David O.","family":"Azorsa","sequence":"first","affiliation":[{"name":"Institute of Molecular Medicine, Phoenix Children's Hospital  Phoenix Arizona"},{"name":"Department of Child Health University of Arizona College of Medicine  Phoenix Arizona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Lee","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine, Phoenix Children's Hospital  Phoenix Arizona"},{"name":"Department of Child Health University of Arizona College of Medicine  Phoenix Arizona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel H.","family":"Wai","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine, Phoenix Children's Hospital  Phoenix Arizona"},{"name":"Department of Child Health University of Arizona College of Medicine  Phoenix Arizona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranjan","family":"Bista","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine, Phoenix Children's Hospital  Phoenix Arizona"},{"name":"Department of Child Health University of Arizona College of Medicine  Phoenix Arizona"},{"name":"Center for Cancer and Blood Disorders Phoenix Children's Hospital  Phoenix Arizona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apurvi R.","family":"Patel","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine, Phoenix Children's Hospital  Phoenix Arizona"},{"name":"Department of Child Health University of Arizona College of Medicine  Phoenix Arizona"},{"name":"Center for Cancer and Blood Disorders Phoenix Children's Hospital  Phoenix Arizona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiman","family":"Aleem","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine, Phoenix Children's Hospital  Phoenix Arizona"},{"name":"Department of Child Health University of Arizona College of Medicine  Phoenix Arizona"},{"name":"Faculty of Science Alexandria University  Alexandria Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael M.","family":"Henry","sequence":"additional","affiliation":[{"name":"Department of Child Health University of Arizona College of Medicine  Phoenix Arizona"},{"name":"Center for Cancer and Blood Disorders Phoenix Children's Hospital  Phoenix Arizona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Arceci","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine, Phoenix Children's Hospital  Phoenix Arizona"},{"name":"Department of Child Health University of Arizona College of Medicine  Phoenix Arizona"},{"name":"Center for Cancer and Blood Disorders Phoenix Children's Hospital  Phoenix 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