Worobec A S, Semere T, Nagata H, Metcalfe D D
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1881, USA.
Cancer. 1998 Nov 15;83(10):2120-9. doi: 10.1002/(sici)1097-0142(19981115)83:10<2120::aid-cncr10>3.0.co;2-c.
The Asp816Val mutation in the catalytic domain of the c-kit receptor has been identified in patients with systemic mastocytosis.
To determine whether this mutation is associated with identifiable clinical patterns of disease and prognosis, a total of 65 patients with mastocytosis were screened for the presence of the Asp816Val mutation in peripheral blood mononuclear cells (PBMCs).
By analysis of HinfI digestion products, the authors found that the overall prevalence of this mutation in the current patient series was 25%. The presence of the Asp816Val mutation in PBMCs was observed in 15 adults (of 16 Asp816Val mutation positive patients) and 1 infant, but not in any children with mastocytosis. Patients whose PBMCs were positive for this mutation (category II and a subset of category Ib mastocytosis patients) manifested a more severe disease pattern, with clinical features ranging in severity from early to advanced myelodysplastic or myeloproliferative syndromes. These patients more commonly had osteosclerotic bone involvement (a clinical feature primarily observed in mastocytosis patients with an associated hematologic disorder) as well as immunoglobulin dysregulation and peripheral blood abnormalities. Furthermore, pedigree analysis of three families provided evidence that the mutation was somatic.
Twenty-five percent of all patients with mastocytosis had the Asp816Val mutation in PBMCs; 56% of these patients had evidence of a myelodysplastic or myeloproliferative syndrome, and 44% had been clinically placed in the indolent mastocytosis category, suggesting that the current classification scheme used to assign prognosis may be inadequate. Therefore, determination of the presence or absence of this mutation in PBMCs of mastocytosis patients offers a useful adjunct in determining the extent of workup and assigning prognosis in this complex and heterogeneous disease.
在系统性肥大细胞增多症患者中已鉴定出c-kit受体催化结构域中的Asp816Val突变。
为了确定该突变是否与可识别的疾病临床模式及预后相关，共对65例肥大细胞增多症患者的外周血单个核细胞（PBMC）进行了Asp816Val突变筛查。
通过对HinfI消化产物的分析，作者发现该突变在当前患者系列中的总体患病率为25%。在16例Asp816Val突变阳性患者中的15例成人和1例婴儿的PBMC中观察到了Asp816Val突变，但在任何肥大细胞增多症儿童中均未观察到。PBMC中该突变呈阳性的患者（II类以及Ib类肥大细胞增多症患者的一个亚组）表现出更严重的疾病模式，临床特征的严重程度从早期到晚期骨髓增生异常或骨髓增殖性综合征不等。这些患者更常出现骨硬化性骨受累（这是主要在伴有血液系统疾病的肥大细胞增多症患者中观察到的临床特征）以及免疫球蛋白失调和外周血异常。此外，对三个家族的系谱分析提供了该突变是体细胞性的证据。
所有肥大细胞增多症患者中有25%的PBMC存在Asp816Val突变；这些患者中有56%有骨髓增生异常或骨髓增殖性综合征的证据，44%在临床上被归类为惰性肥大细胞增多症，这表明目前用于判断预后的分类方案可能不够充分。因此，确定肥大细胞增多症患者PBMC中该突变的有无，对于确定检查范围和判断这种复杂异质性疾病的预后提供了有用的辅助手段。
