ROLE OF C-KIT IN EARLY HEMATOPOISESIS

造血是造血祖细胞经历的过程。 自我更新和分化为各种成熟的血细胞 血统。生长因子-受体的相互作用在 对正常造血的调节，既影响增殖又影响 不同造血系的分化。对这些进行更改 受体在骨髓发育不良和白血病发生中起重要作用。 KIT原癌基因编码酪氨酸激酶跨膜受体 它在非常早期的造血祖细胞上表达，并且是 参与干细胞迁移和分化。增长因素 KIT受体的配体被称为干细胞因子，最近被认为是 纯净的。我们这项研究的目的是调查成长的作用 因子-受体相互作用对造血调控的影响。我们会 通过对KIT受体的研究，探讨KIT受体在造血中的作用 酪氨酸激酶在两种培养细胞系中的表达和活性 从受试者骨髓标本中分离出造血细胞。 KIT受体的表达可以很容易地用单抗进行监测 我们已经研制出的抗体。各种细胞因子的作用， 包括干细胞因子在内，在表达KIT受体的细胞上 学习。最后，我们将查找异常的试剂盒表达和/或功能 在包括白血病在内的血液病患者中， 骨髓增生性疾病和先天性贫血。那些患者的 显示KIT表达或功能异常的细胞将进一步调查 在分子水平上定义缺陷。这些研究应该加强 我们对生长因子-受体相互作用在正常人中作用的了解 和异常的造血状态，从而更好地理解 某些血液疾病的病理生理学，可能还有铅 更好的治疗这些疾病的方法。

Hematopoiesis is the process by which hematopoietic precursor cells undergo self-renewal and differentiation into the various mature blood cell lineages. Growth factor-receptor interactions play a significant role in the regulation of normal hematopoiesis, affecting both proliferation and differentiation of various hematopoietic lineages. Alterations of these receptors plays an important role in myelodysplasia and leukemogenesis. The kit proto-oncogene encodes for a tyrosine-kinase transmembrane receptor that is expressed on very early hematopoietic precursor cells, and is involved in stem cell migration and differentiation. The growth factor ligand for the kit receptor, known as stem cell factor, has been recently purified. The purpose of our study is to investigate the role of growth factor-receptor interactions on the regulations of hematopoiesis. We will investigate the role of the kit receptor in hematopoiesis by studying its expression and tyrosine kinase activity in both cultured cell lines and in hematopoietic cells isolated from bone marrow samples from human subjects. Expression of the kit receptor will be easily monitored using a monoclonal antibody which we have developed. The effects of various cytokines, including stem cell factor, on cells that express the kit receptor will be studied. Finally we will look for abnormal kit expression and/or function in patients with hematological disorders including leukemias, myelodysplastic disorders, and congenital anemias. Those patients whose cells show abnormal kit expression or function will be further investigated to define the defect at the molecular level. These studies should enhance our knowledge of the role of growth factor-receptor interactions in normal and abnormal states o hematopoiesis, thus leading to a better understanding of the pathophysiology of certain hematological diseases, and possibly lead to better therapies for these diseases.