Dror Y, Leaker M, Caruana G, Bernstein A, Freedman M H
Division of Hematology/Oncology, Department of Pediatrics, Research Institute, The Hospital for Sick Children and the University of Toronto, Toronto, Canada.
Br J Haematol. 2000 Mar;108(4):729-36. doi: 10.1046/j.1365-2141.2000.01935.x.
Mastocytosis is characterized by abnormal infiltration of mast cells into various organs. An activating mutation in c-kit, involving an A --> T substitution at nucleotide 2648 has recently been described in some patients with mastocytosis. We describe a 12-year-old girl with this mutation in her bone marrow cells at diagnosis with a myelodysplastic syndrome (MDS) without evidence of mastocytosis, and then in peripheral blood mononuclear cells 1 year later after the emergence of mastocytosis. The role of the c-Kit receptor and its ligand stem cell factor (SCF) in the pathogenesis of the disease was analysed in marrow cell clonogenic assays. We show that the genetic abnormalities in the patient resulted in factor-independent growth and hypersensitivity of primitive progenitors to SCF, with increased production of mast cells. Increased apoptosis and cluster formation, consistent with the myelodysplastic nature of the disorder, accompanied accumulation of abnormal cells with increasing concentrations of SCF.
肥大细胞增多症的特征是肥大细胞异常浸润到各个器官。最近在一些肥大细胞增多症患者中描述了c-kit基因的激活突变，该突变涉及核苷酸2648处的A→T替换。我们描述了一名12岁女孩，诊断为骨髓增生异常综合征（MDS）时其骨髓细胞存在这种突变，当时无肥大细胞增多症证据，1年后出现肥大细胞增多症，其外周血单个核细胞中也出现了这种突变。通过骨髓细胞集落形成试验分析了c-Kit受体及其配体干细胞因子（SCF）在该疾病发病机制中的作用。我们发现，患者的基因异常导致原始祖细胞不依赖因子生长且对SCF高度敏感，肥大细胞产生增加。随着SCF浓度增加，异常细胞积累，同时出现凋亡增加和集落形成，这与该疾病的骨髓增生异常性质相符。
