IN VITRO DETECTION OF RESIDUAL LEUKEMIA

残留白血病的体外检测

• 批准号: 3813028
• 负责人: WILLIAM BENSINGER
• 金额: --
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3813028
• 关键词: T cell receptor; antibody; autologous transplantation; avidin; biotin; blood; blood cell depletion therapy; bone marrow; bone marrow transplantation; circulating neoplastic cell; gel electrophoresis; gene rearrangement; human subject; immunoglobulins; leukemia; lymphocytic leukemia; lymphoma; monoclonal antibody; multiple myeloma; natural gene amplification; neoplasm /cancer diagnosis; neoplasm /cancer relapse /recurrence; nucleic acid hybridization; nucleic acid probes; remission /regression

Current light microscopic techniques are unable to detect small numbers of residual leukemic cells. More sensitive techniques for the detection of residual leukemia are needed in order to allow a more precise definition of remission and a more accurate evaluation of the effectiveness of marrow purging. Recent work has indicated that most lymphoblastic leukemia and lymphomas contain clonal rearrangements of immunoglobulin or T-cell receptor genes. Southern blot analysis can thus detect one malignant cell in 100 normal cells. Avidin-biotin immunoadsorption can be used as a further method for enhancing the ability to detect malignant cells present in the marrow. By combining avidin-biotin immunoadsorption with Southern blot analysis, it is possible to detect clonal rearrangements in as few as one cell in 1,000. Studies outlined in this project will examine the frequency with which clonal gene rearrangements are detectable in marrows obtained from patients with acute lymphoblastic leukemia (ALL) and lymphoma by using Southern blot techniques with and without avidin-biotin immunoadsorption. A prospective study will follow a group of patients with ALL in remission to determine if the presence of clonal gene rearrangements in remission marrows is predictive of relapse. Similar studies will be carried out at the time of marrow storage and at the time of transplant to determine whether the presence of detectable clonal rearrangements is predictive of relapse after AMT for patients with lymphoid malignancies. Once the sensitivity of the assay is determined, these techniques will be used to help monitor the effectiveness of purging myeloma cells from marrow.

目前的光学显微镜技术无法检测到小的 残留白血病细胞的数量。 更敏感的技术， 需要检测残留白血病， 更精确的缓解定义和更准确的评估 骨髓净化的有效性 最近的研究表明， 大多数淋巴母细胞性白血病和淋巴瘤含有克隆 免疫球蛋白或T细胞受体基因重排。 因此，Southern印迹分析可以在100个细胞中检测出一个恶性细胞 正常细胞 抗生物素蛋白-生物素免疫吸附可用作 增强检测恶性细胞能力的另一种方法 存在于骨髓中。 通过结合亲和素-生物素免疫吸附 通过Southern印迹分析，可以检测克隆 只有千分之一的细胞发生重排 概述的研究 在这个项目中，将检查克隆基因 在从病人身上获得的骨髓中可以检测到重排 急性淋巴细胞白血病（ALL）和淋巴瘤， 使用和不使用抗生物素蛋白-生物素的Southern印迹技术 免疫吸附 一项前瞻性研究将跟踪一组 缓解期ALL患者，以确定是否存在 缓解期骨髓中的克隆基因重排可预测 复发 类似的研究将在骨髓移植时进行。 储存和移植时，以确定 可检测到的克隆重排的存在预示着 淋巴系统恶性肿瘤患者AMT后复发。 一旦 测定的灵敏度被确定，这些技术将 用于帮助监测清除骨髓瘤细胞的有效性 从骨髓。