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The complexity of <jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content> makes both the diagnosis and design of response criteria challenging for clinical studies. The tyrosine kinase <jats:styled-content style=\"fixed-case\">KIT<\/jats:styled-content> has been shown to play a crucial role in the pathogenesis of <jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content> and has been a focal point in the development of targeted therapy. Mutations within various domains of the <jats:styled-content style=\"fixed-case\">KIT<\/jats:styled-content> receptor that lead to constitutive activation have been identified in patients, and those involving the activation loop of the <jats:styled-content style=\"fixed-case\">KIT<\/jats:styled-content> receptor are the mutations most frequently detected in patients with mastocytosis. Aberrant activation of the <jats:styled-content style=\"fixed-case\">KIT<\/jats:styled-content> receptor results in increased production of mast cells in extracutaneous organs that may lead to organ failure or early death. This review discusses the diagnosis and management of patients with advanced <jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content>, including the relevance of <jats:styled-content style=\"fixed-case\">KIT<\/jats:styled-content> in this disease, potential therapies targeting this kinase, and criteria for measuring responses to these therapies.<\/jats:p>","DOI":"10.1111\/ejh.12043","type":"journal-article","created":{"date-parts":[[2012,11,27]],"date-time":"2012-11-27T06:12:32Z","timestamp":1353996752000},"page":"89-98","source":"Crossref","is-referenced-by-count":51,"title":["Advanced systemic mastocytosis: the impact of <scp>KIT<\/scp> mutations in diagnosis, treatment, and progression"],"prefix":"10.1111","volume":"90","author":[{"given":"Srdan","family":"Verstovsek","sequence":"first","affiliation":[{"name":"Department of Leukemia The University of Texas MD Anderson Cancer Center Houston TX 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