IMMUNOGLOBULIN GENE ARRANGEMENT EXPRESSION IN LEUKEMIA

描述：(改编自调查人员摘要)总体目标 这项拟议的研究旨在确定该药的潜在临床效用。 白血病患者微小残留病分析及临床意义 了解白血病细胞群在期间和之后的动态 治疗。白血病克隆是由唯一的序列确定的 核苷酸存在于变量、多样性和 连接免疫球蛋白(LG)和T细胞受体(TCR)基因的区域。 聚合酶链式反应扩增重排 然后与含有该基因的寡核苷酸探针杂交 白血病细胞LG或TCR基因的连接序列允许 调查人员将确定来自白血病克隆的细胞是否 以及他们所代表的总数的大约百分比。 B前体细胞急性白血病患者的基因重排 淋巴细胞白血病(ALL)的碱基对率高于预期 从生殖系序列的变化，表明也许体细胞突变 发生在LG的表面显示之前。确定聚合酶链式反应是否 基因重排的分析有助于追踪残留病和 早期B祖细胞是否发生体细胞突变 提出了具体的目标：1)检验假设 白血病克隆在治疗的前三个月中消失 可用于预测性地确定风险组。骨髓样本 在患者确诊后的头三个月内服用 将对接受不同化疗方案治疗的患者进行分析 聚合酶链式反应的残留病程度。将包括患有高血压症和 低风险特征，以及不同种族背景的患者 确定是否存在基于种族的药物敏感性差异。2)测试 维持期间残留疾病水平分析的假设 治疗可以识别即将复发的情况。初步数据表明，聚合酶链反应 对骨髓样本的分析可以确定即将发生的复发，但不能 进行了大规模的前瞻性研究。骨髓样本将 每隔三个月进行一次残留疾病分析，并确定是否 复发是可以准确预测的。3)继续研究这种可能性 体细胞突变发生在前B细胞和早期B祖细胞中 急性淋巴细胞性白血病。4)开发自动量化的方法 残留的白血病。成功完成的具体目标有 预计将提供相当大的新洞察力，了解 在治疗期间白血病细胞的数量，并将决定是否聚合酶链式反应 残留疾病的测定是临床上有用的工具，在此基础上 未来的临床试验可以作为基础。

DESCRIPTION: (adapted from the investigator's abstract) The overall goal of the proposed research is to determine the potential clinical utility of the analysis of minimal residual disease in patients with leukemia, and to understand the dynamics of the leukemic cell population during and following treatment. The leukemic clone is identified by the unique sequence of nucleotides present at the junction(s) of the variable, diversity, and joining regions of the immunoglobulin (lg) and T cell receptor (TCR) genes. Amplification of rearrangements by the polymerase chain reaction (PCR) followed by hybridization with an oligonucleotide probe containing the junctional sequences from the leukemic cell lg or Tcr gene allows the investigators to determine whether the cells from the leukemic clone are present, and the approximate percentage of the total that they represent. The rearranged genes from the patients with B precursor cell acute lymphoblastic leukemia (ALL) show a higher than expected rate of base pair changes from the germline sequence, indicating that perhaps somatic mutation is occurring prior to surface display of lg. To determine whether PCR analysis of gene rearrangements is useful in tracking residual disease and whether somatic mutation occurs in early B progenitor cells the following specific aims are proposed: 1) Test the hypothesis that the kinetics of disappearance of the leukemic clone during the first three months of therapy can be used prognostically to determine risk groups. Bone marrow samples taken during the first three months following diagnosis from patients being treated with various chemotherapeutic regimens will be analyzed for the extent of residual disease of PCR. Included will be patients with high and low risk features, and patients of different racial backgrounds, to determine if there are race-based differences in drug sensitivity. 2) Test the hypothesis that analysis of residual disease levels during maintenance therapy can identify impending relapse. Preliminary data indicate that PCR analysis of bone marrow samples can identify impending relapse, but no large-scale prospective study has been performed. Bone marrow samples will be analyzed at three month intervals for residual disease and determine if relapse can accurately be predicted. 3) Continue to examine the possibility that somatic mutation is occurring in pre-B and early B progenitor cell acute lymphoblastic leukemia. 4) Develop methods to automate quantitation of residual leukemia. Successful completion of the specific aims are expected to provide considerable new insight into the dynamics of the leukemic cell population during therapy, and will determine whether PCR determination of residual disease is a clinically useful tool upon which future clinical trials can be based.