A novel form of mastocytosis associated with a transmembrane c-kit mutation and response to imatinib
A novel form of mastocytosis associated with a transmembrane c-kit mutation and response to imatinib
复制标题
DOI：
10.1182/blood-2003-11-3816
复制
发表时间：
2004-04-15
期刊：
影响因子：
20.3
通讯作者：
Metcalfe, DD
中科院分区：
文献类型：
--
作者：
Akin, C;Fumo, G;Metcalfe, DD
在一个病人的c-kit基因的突变分析与以前未描述的肥大细胞疾病的变异揭示了种系突变，Phe 522 Cys，在跨膜部分的试剂盒受体蛋白。转染实验表明，突变引起配体非依赖性的自磷酸化的试剂盒，这是抑制酪氨酸激酶抑制剂甲磺酸伊马替尼。该患者的骨髓活检和穿刺显示出独特的病理特征，存在过多的成熟肥大细胞，并且不存在异常肥大细胞表面表达的CD 2、CD 25和C1335。甲磺酸伊马替尼治疗导致肥大细胞负荷和临床症状的显着改善。这些结果突出了跨膜区的试剂盒在激活的分子及其在肥大细胞发育的重要性的意义，并建议在肥大细胞增多症患者中筛选跨膜c-kit突变的作用与决定使用甲磺酸伊马替尼。(C)2004年，美国血液学会。
Mutational analysis of the c-kit gene in a patient with a previously undescribed variant of mast cell disease revealed a germline mutation, Phe522Cys, within the transmembrane portion of the Kit receptor protein. Transfection experiments revealed that the mutation caused ligand-independent autophosphorylation of Kit, which was inhibited by the tyrosine kinase inhibitor imatinib mesylate. The patient's bone marrow biopsy and aspirate displayed unique pathologic features with the presence of excessive numbers of mature-appearing mast cells and absence of aberrant mast cell surface expression of CD2, CD25, and C1335. Therapy with imatinib mesylate resulted in a dramatic improvement in mast cell burden and clinical symptoms. These results highlight the significance of the transmembrane region of Kit in activation of the molecule and its importance in mast cell development and suggest a role for screening for transmembrane c-kit mutations in patients with mastocytosis in association with the decision to use imatinib mesylate. (C) 2004 by The American Society of Hematology.