ABNORMAL TERMINAL TRANSFERASE BIOSYNTHESIS IN REMISSION

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 骨髓液。白血病细胞的生物合成速率是可以测量的。 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 人类TDT特定消息将被用来建立关联 RNA合成的最高速率、mRNA和蛋白质的稳定水平 生物合成。这些测量将扩展到异质模型 人群和临床样本。这些检测方法的预后价值 会通过将化验应用于临床常规样本进行检测 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 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.