title: Functional deregulation of KIT: link to mast cell proliferative diseases and other neoplasms.
abstract: In this review, the authors discuss common gain-of-function mutations in the stem cell factor receptor KIT found in mast cell proliferation disorders and summarize the current understanding of the molecular mechanisms by which these transforming mutations may affect KIT structure and function leading to altered downstream signaling and cellular transformation. Drugs targeting KIT have shown mixed success in the treatment of mastocytosis and other hyperproliferative diseases. A brief overview of the most common KIT inhibitors currently used, the reasons for the varied clinical results of such inhibitors and a discussion of potential new strategies are provided.
authors.affiliation: Mast Cell Biology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, 10 Center Drive, Building 10, Room 11C207, MSC 1881, Bethesda, MD 20892, USA.
authors.forename: Glenn
authors.initials: G
authors.lastname: Cruse
authors.affiliation: Mast Cell Biology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, 10 Center Drive, Building 10, Room 11C207, MSC 1881, Bethesda, MD 20892, USA.
authors.forename: Dean D
authors.initials: DD
authors.lastname: Metcalfe
authors.affiliation: Mast Cell Biology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, 10 Center Drive, Building 10, Room 11C207, MSC 1881, Bethesda, MD 20892, USA. Electronic address: Ana.Olivera@nih.gov.
authors.forename: Ana
authors.initials: A
authors.lastname: Olivera
mesh_terms: D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D005091:Exons; D015972:Gene Expression Regulation, Neoplastic; D019337:Hematologic Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008415:Mastocytosis / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D019089:Stem Cell Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit
keywords: KIT inhibitors; KIT mutations; KIT signaling; KIT trafficking; Mastocytosis
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