ABNORMAL TERMINAL TRANSFERASE BIOSYNTHESIS IN REMISSION

缓解期末端转移酶生物合成异常

• 批准号: 3184272
• 负责人: ALLEN Edgar SILVERSTONE
• 金额: $ 12.23万
• 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 1986-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3184272
• 关键词: DNA directed DNA polymerase; adult human (21+); bone marrow exam; cancer registry /resource; cellular oncology; child (0-11); human tissue; leukemia; myelogenous leukemia; neoplasm /cancer diagnosis; neoplasm /cancer remission /regression; neoplastic cell; pediatric neoplasm /cancer; phosphorylation; radiotracer; 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 embodied in biochemical, immunofluorescent, and antibody affinity assays, the dynamic quality of rate of TdT biosynthesis will be utilized to discriminate between normal and leukemic TdT-positive marrow populations. The biosynthesis rate by leukemic cells is measureably greater than the rate of synthesis by equivalent numbers of normal TdT positive cells in bone marrow. As a further refinement, cDNA probes for TdT-specific message will be utilized in model studies to establish correlations between rates of RNA synthesis, steady-state levels of mRNA, and protein biosynthesis. These measurements will be extended to heterogeneous model populations and, ultimately, clinical samples. The prognostic value of these assays will be determined by applying the assays to routine clinical samples from leukemia 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技术。 检测有核细胞总数中是否存在0.5%至1%的白血病细胞 利用差异合成速率进行骨髓细胞群的研究 模板非依赖的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描述的 稳态测量体现在生化、免疫荧光和 抗体亲和力测定TDT生物合成率的动态质量 将被用来区分正常和白血病TDT阳性 骨髓种群。白血病细胞的生物合成速率是可测量的 比合成速度快相当于正常TDT的数目 骨髓中有阳性细胞。作为进一步的改进，cdna探针用于 将在模型研究中利用特定于TDT的信息来确定 核糖核酸合成速率、稳态信使核糖核酸水平 和蛋白质的生物合成。这些测量将扩展到 不同的模型人群，最终是临床样本。这个 这些检测的预后价值将通过应用这些检测来确定。 对白血病患者的常规临床样本进行治疗或停药 治疗和缓解期间，已经或可能发展为TDT阳性的人 疾病。