Abstract
Mutations causing constitutive activation of KIT have been shown to be causative in some forms of mastocytosis, and several types of mutations have been associated with myeloproliferative disorders (MPDs), acute myelogenous leukemia (AML), sinonasal lymphomas, and gastrointestinal stromal tumors (GIST). We divide these activating mutation into two types - 'regulatory type' mutations, which affect regulation of the kinase molecule, and 'enzymatic pocket type' mutations, which alter the amino acid sequence directly forming the enzymatic site. KIT inhibitors have been suggested as therapeutic drugs for these conditions, but different types of activating mutations respond differentially to KIT inhibitors, so classification of individuals on the basis of specific mutations is necessary to guide therapy.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
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Review
MeSH terms
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Acute Disease
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Adult
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Binding Sites
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Child
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Drug Design
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Enzyme Activation / genetics
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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Gastrointestinal Neoplasms / genetics
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Hematologic Neoplasms / genetics
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Humans
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Leukemia, Myeloid / genetics
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Ligands
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Lymphoma, Non-Hodgkin / genetics
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Mastocytosis / classification
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Mastocytosis / drug therapy
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Mastocytosis / genetics*
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Mesenchymoma / genetics
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Mutation*
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Myeloproliferative Disorders / genetics
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Nose Neoplasms / genetics
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Paranasal Sinus Neoplasms / genetics
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Phosphorylation
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Protein Processing, Post-Translational
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Proto-Oncogene Proteins c-kit / drug effects
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Proto-Oncogene Proteins c-kit / genetics*
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Proto-Oncogene Proteins c-kit / metabolism
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Stem Cell Factor / antagonists & inhibitors
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Stem Cell Factor / physiology
Substances
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Antineoplastic Agents
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Enzyme Inhibitors
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Ligands
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Stem Cell Factor
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Proto-Oncogene Proteins c-kit