ROLE OF C-KIT IN EARLY HEMATOPOISESIS

C-KIT 在早期造血中的作用

• 批准号: 3087836
• 负责人: Carlos M. De Castro
• 金额: $ 8.8万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-07-01 至 1996-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3087836
• 关键词: anemia; bone marrow exam; cytokine; dyserythropoietic anemia; erythroleukemia; flow cytometry; gene expression; genetic promoter element; growth factor receptors; hematopoiesis; hematopoietic growth factor; hematopoietic stem cells; human fetus tissue; human subject; human tissue; immunoprecipitation; leukemia; luciferin monooxygenase; monoclonal antibody; polymerase chain reaction; protein tyrosine kinase; protooncogene; radioimmunoassay; receptor expression; reporter genes; tissue /cell culture; western blottings

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.

造血是造血前体细胞进行造血的过程 自我更新和分化成各种成熟血细胞 血统。 生长因子-受体相互作用在 正常造血的调节，影响增殖和 各种造血谱系的分化。 这些的改变 受体在骨髓增生异常和白血病发生中起重要作用。 该试剂盒原癌基因编码酪氨酸激酶跨膜受体 在非常早期的造血前体细胞上表达，并且是 参与干细胞迁移和分化。 生长因子 该试剂盒受体的配体，称为干细胞因子，最近已被 纯化的。 我们研究的目的是调查增长的作用 因子-受体相互作用对造血调节的影响。 我们将 通过研究 Kit 受体在造血中的作用 培养细胞系和细胞中的表达和酪氨酸激酶活性 从人类受试者的骨髓样本中分离出的造血细胞。 使用单克隆抗体可以轻松监测试剂盒受体的表达 我们开发的抗体。 各种细胞因子的作用， 包括干细胞因子，在表达试剂盒受体的细胞上将 研究过。 最后我们将寻找异常的试剂盒表达和/或功能 患有血液疾病（包括白血病）的患者， 骨髓增生异常性疾病和先天性贫血。 那些患者 细胞表现出异常的试剂盒表达或功能将进一步研究 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情况下的作用的了解 和造血异常状态，从而更好地了解 某些血液疾病的病理生理学，并可能导致 以便更好地治疗这些疾病。