MATURATION INDUCTION OF HUMAN LEUKEMIC CELLS

人类白血病细胞的成熟诱导

• 批准号: 3173515
• 负责人: J. W. none CHIAO
• 金额: $ 15.42万
• 依托单位: NEW YORK MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-03-01 至 1989-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3173515
• 关键词: T lymphocyte; affinity chromatography; antibody formation; antileukemic agent; athymic mouse; autoradiography; blood cell count; cell differentiation; cell growth regulation; cell type; electrofocusing; flow cytometry; gel electrophoresis; gel filtration chromatography; growth factor; growth inhibitors; growth media; hematopoietic growth factor; histochemistry /cytochemistry; human subject; human tissue; hybridomas; immunofluorescence technique; ion exchange chromatography; leukocyte activation /transformation; leukopoietic factor; lymphocyte; lymphokines; monoclonal antibody; myelogenous leukemia; neoplasm /cancer immunotherapy; neoplasm /cancer transplantation; tissue /cell culture

A physiological factor, the maturation inducer (MI, m.w. 50,000), produced by T cells and capable of inducing the differentiation and maturation of human myeloid leukemia cells has been described. It has been demonstrated to be distinct from the commonly known lymphokines and may be the human counterpart of the murine differentiation factor MGI2 for myeloid leukemia cells. It has been demonstrated media in vitro and in vivo growth suppressioin and differentiation of leukemia cells. With the available MI molecules and specific monoclonal antibodies, we plan to investigate the differentiation blocks and defects in leukemia, and to evaluate differentiation indunction as a corrective approach. The quantitation of serum MI level in leukemia patients and normal persons will be compared by an ELISA method using antibodies. An assessment will be made as to whether there is a lack of MI in patients. Immunofluorescent antibody techniques will be used to quantitate the MI producing lymphocytes. The level of producing cells in normal persons has been determined and an assessment can be made as to whether there is a lack of these cells in patients. Furthermore, cell-MI interactions will be studied by analyzing the number of membrane receptors and binding specificity. The effectivity of the interaction of leukemia cells with the MI will be revealed. Myeloid leukemia cells have been shown to be induced to differentiation normally by the maturation inducer, suggesting the use of MI stimulation of the production of MI in vivo, or the use of MI-producing cells as grafts. Patient lymphocytes will be cultured with IL2 to assess MI production and the growth of the producing cells as an autologous source. Large quantities of MI will be prepared by cell lines constitutively producing MI, and by T-T cell hybridomas, using affinity chromatography, etc. The proposed research will reveal the basis of leukogenesis and provide crucial information for corrective approaches.

生理因素，成熟诱导剂(MI，M.W.50,000)，制作 由T细胞激活，并能诱导其分化成熟 人类髓系白血病细胞已被描述。它已经被证明了 与常见的淋巴因子不同，可能是人类 髓系白血病小鼠分化因子MGI2的类似物 细胞。已证实在体外和体内培养基均有生长。 抑制和分化白血病细胞。 利用可用的MI分子和特定的单抗，我们计划 目的：研究白血病的分化障碍和缺陷。 评估差异化抑制作为一种纠正方法。这个 白血病患者和正常人血清MI水平的定量检测 通过使用抗体的ELISA法进行比较。一项评估将是 对于患者是否存在心肌梗死的缺失进行了探讨。免疫荧光 抗体技术将被用来量化MI的产生 淋巴细胞。正常人产生细胞的水平一直是 确定并可以评估是否缺乏 患者体内的这些细胞。此外，还将研究细胞-MI相互作用 通过分析膜受体的数量和结合的特异性。这个 白血病细胞与MI的相互作用的有效性将是 被揭露了。 髓系白血病细胞已被证明可被诱导分化 通常由成熟诱导剂诱导，提示使用MI刺激 在体内产生心肌梗死，或使用产生心肌梗死的细胞作为移植物。 患者淋巴细胞将与IL2一起培养，以评估MI的产生和 作为自体来源的生产细胞的生长。大型 大量的MI将由构成生产的细胞系来制备 MI、T-T细胞杂交瘤、亲和层析等。 拟议的研究将揭示白血病发生的基础，并提供关键的 纠正方法的信息。