Immunoglobulin Gene Arrangement/Expression in Leukemia

白血病中的免疫球蛋白基因排列/表达

• 批准号: 6436634
• 负责人: Geoffrey A. Neale
• 金额: $ 21.32万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-07-01 至 2006-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6436634
• 关键词: acute lymphocytic leukemia; antigen receptors; biomedical automation; cadherins; clinical research; diagnosis design /evaluation; gene expression; gene rearrangement; human subject; immunoglobulin genes; minimal residual disease; neoplasm /cancer diagnosis; neoplasm /cancer genetics; polymerase chain reaction

DESCRIPTION (provided by applicant): By identifying patients at high risk of relapse, residual disease assessment promises to increase the cure rate of children with acute lymphoblastic leukemia (ALL). The quantity of residual, morphologically undetectable disease (minimal residual disease or MRD) present during therapy is an independent predictor of patient outcome. Although polymerase chain reaction assays can quantify MRD, simpler methods are needed for clinical application. In the previous funding period, simple automated fluorescence detection assays were developed for quantification of B- and T-cell antigen receptor gene rearrangements, which can be used as leukemia-specific markers in 90 percent of ALL cases. The studies now proposed will determine the utility of these assays for quantification of leukemic cells in clinical samples (Aim 1). Universally applicable ALL markers are also needed for the integration of MRD assays into clinical protocols. Our previous studies showed that the neural gene, R-cadherin, is ectopically expressed in ALL but not in normal hematopoietic cells. Expression of R-cadherin should serve as a marker of recurrent leukemic cells and as an indicator of treatment-refractory ALL. The proposed studies will determine whether expression of R-cadherin can identify patients at a high risk of relapse and evaluate the efficacy of therapy (Aim 2). The application of ultra-sensitive MRD assays can be used to address an emerging problem in the treatment of ALL. Current intensive therapy has caused a delay in the timing of hematologic relapse. Assessment of MRD at end of therapy should permit identification of those patients with greatest risk of post-therapy relapse (Aim 3). The development of new automated MRD assays and the identification of new markers of leukemia should improve residual disease evaluation and thereby improve risk-directed therapy selection for every child with ALL.

描述（由申请人提供）：通过识别高风险患者， 复发，残留疾病评估有望提高治愈率， 儿童急性淋巴细胞白血病（ALL）。残留量， 存在形态学无法检测到的疾病（微小残留病或MRD） 是患者预后的独立预测因素。虽然 聚合酶链反应测定可以定量MRD，需要更简单的方法 用于临床应用。在上一个供资期间，简单的自动化 开发了荧光检测分析用于定量B-和 T细胞抗原受体基因重排，其可用作 90%的ALL病例都有白血病特异性标志物。目前提出的研究 将确定这些测定用于定量白血病细胞的效用 在临床样品中（目标1）。 整合MRD还需要普遍适用的ALL标志物 临床试验方案。我们之前的研究表明， R-cadherin基因在ALL中异位表达，而在正常人中不表达。 造血细胞R-cadherin的表达应该作为一个标志， 复发性白血病细胞和作为治疗难治性ALL的指标。的 拟议的研究将确定R-钙粘蛋白的表达是否可以识别 复发风险高的患者，并评估治疗的疗效（目的 2）。 超灵敏MRD测定的应用可用于解决 急性淋巴细胞白血病治疗中的新问题。目前的强化治疗导致 血液学复发的时间延迟。 治疗结束时的MRD评估应允许识别 治疗后复发风险最大的患者（目标3）。的发展 新的自动化MRD测定和白血病新标志物的鉴定 应改善残留疾病的评估，从而提高风险导向 为所有ALL患儿选择治疗方案。