Classes of c-KIT activating mutations:: proposed mechanisms of action and implications for disease classification and therapy
Classes of c-KIT activating mutations:: proposed mechanisms of action and implications for disease classification and therapy
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DOI：
10.1016/s0145-2126(01)00028-5
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发表时间：
2001-07-01
影响因子：
2.7
通讯作者：
Ma, YS
中科院分区：
文献类型：
--
作者：
Longley, BJ;Reguera, MJ;Ma, YS
导致KIT结构性激活的突变被证明是导致某些形式的肥大细胞增多症的原因，几种类型的突变与骨髓增生性疾病(MPDS)、急性髓细胞白血病(AML)、鼻窦淋巴瘤和胃肠道间质瘤(GIST)有关。我们将这些激活突变分为两种类型--影响激酶分子调节的“调节型”突变和直接改变形成酶位点的氨基酸序列的“酶口袋型”突变。KIT抑制剂已被建议作为治疗这些疾病的药物，但不同类型的激活突变对KIT抑制剂的反应不同，因此有必要根据特定突变对个体进行分类，以指导治疗。(C)2001爱思唯尔科学有限公司。保留所有权利。
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. (C) 2001 Elsevier Science Ltd. All rights reserved.