Bead-array for rapid risk-stratification in leukemia

描述（由申请人提供）：白血病是一组血癌，其特征是发育中的白色血细胞不受控制地生长。癌细胞的积累会干扰身体产生健康的血细胞，从而削弱对感染的免疫反应。在全球范围内，估计每年诊断出257，000例新的白血病病例，每年约有195，000例死亡。根据美国癌症协会的数据，2003年美国报告了30，800例所有类型的白血病新病例。白血病是儿童和20岁以下年轻人死于癌症的头号原因。用于对白血病患者进行分类的最重要的实验室特征之一是白血病原始细胞内的特定染色体易位，其用于选择可能提供最佳结果的治疗方案。由易位形成的融合蛋白被认为有助于白血病的发展和进展，因此是治疗靶点以及诊断标志物。新的治疗方法可能会进一步增加识别特定白血病相关易位的重要性，以确定最有效的治疗过程。带有流式细胞仪检测的液珠阵列特别适合诊断实验室的要求，并将成为我们使用Luminex xMAP技术平台进行多重检测的基础。这种形式通常应用于临床分析物，包括血清学、遗传学和传染病靶标。该项目的I期资金支持成功开发了一种快速单管测定法，用于使用融合转录物作为标记物（21种融合转录物标记物）同时检测白血病相关染色体易位。I期研究还显示了用于试验临床实施的综合控制系统的可行性。因此，我们推出了一种试剂盒（仅供研究使用，RUO），用于快速检测来自最常见的白血病相关易位的12种融合转录标志物，商品名为Signature LTx Leukemia Translocation Panel。拟议的II期项目的最终目标是调整和扩展该检测试剂盒，使其成为一种稳健的、高通量的临床诊断试剂盒，用于白血病的快速风险分层。第二阶段的具体目标是：1。扩大检测范围，以纳入其他临床相关标志物。2.为该检测试剂盒的临床试验开发一个全面的检测试剂盒控制系统。3.我们的快速白血病亚型分型（危险分层）检测系统的临床评价。本提案的总体目标是开发一种用于白血病亚型分型和风险分层的检测试剂盒（Signature LTx）。该测定的这种液体珠阵列形式将为诊断实验室提供效率和成本效益，并为医生和患者提供用于做出治疗决策的关键信息。

DESCRIPTION (provided by applicant): Leukemia is a set of blood cancer characterized by the uncontrolled growth of developing white blood cells. The accumulation of cancerous cells interferes with the body's production of healthy blood cells therefore impairing immune response to infection. Worldwide, an estimated 257,000 new cases of leukemia are diagnosed each year, with approximately 195,000 deaths annually. According to the American Cancer Society, 30,800 new cases of all types of leukemia were reported in the US in 2003. Leukemia is the number one cause of deaths from cancer in children and young adults under age 20. One of the most important laboratory features used to categorize leukemia patients is the specific chromosomal translocations within the leukemia blasts, which are used to choose the therapeutic options that are likely to provide the best outcomes. Fusion proteins formed by the translocations are thought to contribute to the development and progression of leukemia and are thus therapeutic targets as well as diagnostic markers. New therapeutic approaches are likely to further increase the importance of identifying specific leukemia-associated translocations in order to determine the most effective course of treatment. Liquid bead arrays with flow cytometry detection are particularly suited to the requirements of the diagnostic laboratory and will be the basis for our multiplex detection assay using the Luminex xMAP technology platform. This format has been generally applied to clinical analytes, including serologic, genetic, and infectious disease targets. Phase I funding for this project supported the successful development of a rapid single-tube assay for simultaneous detection of leukemia-associated chromosome translocations using fusion transcripts as markers (21 fusion transcript markers). The phase I study also showed the feasibility of a comprehensive control system for use in clinical implementation of the assay. As a result we have launched a kit (for Research Use Only, RUO) for rapid detection of 12 fusion transcript markers from most common leukemia-associated translocations under the trade name Signature LTx Leukemia Translocation Panel. The ultimate goal of proposed phase II project is to adapt and expand this assay into a robust, high-throughput clinic diagnostic kit for rapid risk-stratification in leukemia. Specific Aims of Phase II are: 1. Expand the assay to include additional clinically relevant markers. 2. Develop a comprehensive assay control system for clinical test of this assay. 3. Clinical evaluation of our assay system for rapid leukemia subtyping (risk stratification). The overall goal of this proposal is to develop an assay (Signature LTx) for subtyping and risk-stratification of leukemia. This liquid bead array format of this assay will provide efficiency and cost benefits to diagnostic laboratories and provide crucial information to physicians and patients for use in making treatment decisions.