THE PATHOGENESIS, DIAGNOSIS, AND TREATMENT OF SYSTEMIC MAST CELL DISORDERS

肥大细胞增生症是一种肥大细胞增生紊乱的疾病。它影响所有年龄、性别和所有种族群体。在某些情况下，肥大细胞增多症具有侵袭性并最终致命。因此，我们的努力是为了改善诊断和治疗；并澄清这种疾病的病因。治疗侵袭性疾病的成功方法仍然难以捉摸。然而，患有惰性肥大细胞增多症的妇女有正常的怀孕和分娩，她们的孩子不受影响。我们在肥大细胞增多症患者中首次发现的c-kit和激活突变（Asp816Val; Asp816Tyr）的相关性研究仍在继续。现在的数据表明，所有成年肥大细胞增多症患者在一些外周血细胞和皮肤病变中都有816点突变。相比之下，患有肥大细胞增多症的儿科患者可能仅在皮肤病变中表现出这种突变；在一些儿童中，c-kit没有突变。分子研究与Asp816Val突变是体细胞突变而不是生殖系组织的结论一致。血浆CD117 （KIT）和CD25水平是疾病活动性的有用替代标志物；并帮助选择需要接受骨髓活检的儿童。

Mastocytosis is a disease of disordered mast cell proliferation. It affects all ages, both sexes, and all ethnic groups. In some cases, mastocytosis has an aggressive and ultimately fatal course. Thus, our efforts are directed to improving diagnosis and treatment; and to clarifying the etiology of this disease. A successful approach to treatment for aggressive disease remains elusive. However, women with indolent mastocytosis have normal pregnancies and deliveries and their children are not affected. Studies on c-kit and the relevance of activating mutations which we first identified (Asp816Val; Asp816Tyr) in mastocytosis patients are continuing. Data now indicates all adult patients with mastocytosis appear to have the point mutation at position 816 in some peripheral blood cells and in skin lesions. In contrast, pediatric patients with mastocytosis may demonstrate this mutation only in skin lesions; and in some children no mutation in c-kit can be identified. Molecular studies are consistent with the conclusion that the Asp816Val mutation is a somatic mutation and is not in germ line tissues. Plasma levels of CD117 (KIT) and CD25 are useful surrogate markers of disease activity; and aid in the selection of children who should undergo a bone marrow biopsy.