Immunoglobulin Gene Arrangement/Expression in Leukemia

描述(由申请人提供)：通过识别高危患者 复发，残留病评估有望提高治愈率 儿童急性淋巴细胞白血病(ALL)。残留物的数量， 存在形态上无法检测的疾病(微小残留病或MRD) 在治疗过程中是患者预后的独立预测因素。虽然 聚合酶链式反应可以定量检测MRD，需要更简单的方法 用于临床应用。在上一个资助期，简单自动化 建立了B-和B-的荧光检测方法 T细胞抗原受体基因重排，可作为 在所有病例中，有90%是白血病特异性标志物。现在建议进行的研究 将决定这些化验方法在白血病细胞量化方面的效用 在临床样本中(目标1)。 普遍适用的所有标记物也是整合MRD所必需的 化验成临床方案。我们之前的研究表明，神经 R-钙粘附素基因在ALL中异位表达，但在正常组织中不表达 造血细胞。R-钙粘附素的表达可作为卵巢癌的标志物 复发的白血病细胞和作为治疗难治性ALL的指标。这个 拟议的研究将确定R-钙粘附素的表达是否可以识别 复发风险高的患者并评估治疗效果(目的 2)。 应用超灵敏的MRD分析可用于解决 在治疗ALL方面出现了新的问题。目前的强化治疗已经导致 血液病复发时间的延迟。 治疗结束时对MRD的评估应允许识别 治疗后复发风险最高的患者(目标3)。的发展。 新的自动MRD检测方法和白血病新标志物的鉴定 应改进残留病评估，从而改进风险导向 为每一位ALL儿童选择治疗方案。

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.