Bead-array for rapid risk-stratification in leukemia

描述(申请人提供)：白血病是一组以发育中的白细胞不受控制地增长为特征的血癌。癌细胞的积累干扰了人体生产健康的血细胞，从而削弱了对感染的免疫反应。在世界范围内，估计每年有257,000例新的白血病病例被诊断出来，每年大约有195,000人死亡。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。白血病是导致20岁以下儿童和年轻人癌症死亡的头号原因。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中的特定染色体易位，这些易位被用来选择可能提供最佳结果的治疗方案。易位形成的融合蛋白被认为有助于白血病的发生和发展，因此是治疗的靶点和诊断标记。新的治疗方法可能会进一步提高识别特定的白血病相关易位的重要性，以便确定最有效的疗程。带有流式细胞仪检测的液体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。这种形式已广泛应用于临床分析，包括血清学、遗传学和传染病靶标。该项目的第一阶段资金支持成功地开发了一种快速单管检测方法，使用融合转录本作为标记物(21个融合转录物标记物)同时检测白血病相关的染色体易位。第一阶段的研究也显示了一套全面的控制系统应用于临床检测的可行性。因此，我们推出了一种试剂盒(仅供研究使用，RUO)，用于快速检测最常见的白血病相关易位的12个融合转录标志物，商标为Signature LTX白血病易位小组。拟议的第二阶段项目的最终目标是将该检测方法调整和扩展为一种强大的、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，纳入更多的临床相关标记物。2.建立一套全面的检测控制系统，用于该检测方法的临床检验。3.白血病快速分型检测系统的临床评价(风险分层)。这项建议的总体目标是开发一种用于白血病亚型和风险分层的分析方法(Signature LTX)。这种检测的液体微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关键信息，用于制定治疗决策。

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.