ABNORMAL TERMINAL TRANSFERASE BIOSYNTHESIS IN REMISSION

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， 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 骨髓细胞 白血病细胞的生物合成速率是可测量的 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， TdT特异性信息将用于模型研究，以建立 RNA合成速率，mRNA稳态水平， 和蛋白质生物合成。 这些测量将扩展到 异质模型群体和最终的临床样品。 的 这些测定的预后价值将通过应用这些测定来确定 常规临床样本来自白血病患者的治疗，或关闭 治疗和缓解期，已经或可能发展为TdT阳性 疾病

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.