ABNORMAL TERMINAL TRANSFERASE BIOSYNTHESIS IN REMISSION

缓解期末端转移酶生物合成异常

• 批准号: 3184273
• 负责人: ALLEN Edgar SILVERSTONE
• 金额: $ 10.76万
• 依托单位: UPSTATE MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-30 至 1988-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3184273
• 关键词: DNA directed DNA polymerase; bone marrow exam; cancer registry /resource; cellular oncology; child (0-11); human tissue; leukemia; messenger RNA; myelogenous leukemia; neoplasm /cancer diagnosis; neoplasm /cancer remission /regression; neoplastic cell; pediatric neoplasm /cancer; phosphorylation; radiotracer; synchronous cell division; tissue /cell culture

The objective of this research is the development and utilization of assays to detect the presence of 0.5 to 1% leukemic cells in the total nucleated bone marrow cell population by utilizing the differential rate of synthesis of the template independent DNA polymerase terminal deoxynucleotidyl transferase (TdT). Rather than utilizing the already well-characterized steady-state measurements embodies in biochemical, immunofluoresecent, and antibody affinity assays, the dynamic quality of rate of TdT biosynthesis will be utilized to discriminate between normal and leukemic TdT-positive marrow poulations. The biosynthesis rate by leukemic cells is measurably greater than the rate of synthesis by equivalent numbers of normal TdT positive cells in bone marrow. As a further refinement, cDNA probes for human TdT-specific message will be utilized to establish correlations beweeen rate of RNA synthesis, steady-state levels of mRNA, and protein biosynthesis. These measurements will be extended to heterogeneous model populations and clinical samples. The prognostic value of these assays will be determned by applying the assays to routine clincal samples from leukemic patients in treatment, or off treatment and in remission, who have had, or might develop, TdT-positive disease.

本研究的目的是开发和利用检测方法 检测总有核细胞中0.5 - 1%白血病细胞的存在， 利用差别合成率的骨髓细胞群 模板非依赖性DNA聚合酶末端脱氧核苷酸 转移酶（TdT）。 而不是利用已经很好地表征的 稳态测量体现在生化、免疫荧光和 抗体亲和力测定，TdT生物合成速率的动态质量 将用于区分正常和白血病TdT阳性 骨髓增生 白血病细胞的生物合成率是可测量的 比正常TdT的等量合成率高 骨髓中的阳性细胞。 作为进一步的改进，使用cDNA探针， 将利用人类TdT特异性信息来建立相关性 在RNA合成速率、mRNA和蛋白质的稳态水平之间 生物合成 这些测量方法将被推广到异构模型 人群和临床样本。 这些检测的预后价值 将通过对来自以下地区的常规临床样本进行检测来确定 正在接受治疗或停止治疗和缓解的白血病患者， 患有或可能患有TdT阳性疾病