Bead-array for rapid risk-stratification in leukemia

用于白血病快速风险分层的微珠阵列

• 批准号: 7290966
• 负责人: FEI YE
• 金额: $ 46.56万
• 依托单位: AMBION DIAGNOSTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-15 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7290966
• 关键词: Address; Age; American Cancer Society; Biological Assay; Biological Markers; Biotin; Blast Cell; Blood Cells; Blood specimen; Bone Marrow; Cancer Center; Cancerous; Capital; Cause of Death; Cells; Cessation of life; Chemicals; Child; Chimeric Proteins; Chromosomal translocation; Chronic Myeloid Leukemia; Clinic; Clinical; Clinical Trials; Collaborations; Color; Communicable Diseases; Computer software; Costs and Benefits; Coupled; Coupling; Data; Detection; Development; Diagnosis; Diagnostic; Diagnostic tests; Doctor of Medicine; Dyes; Ensure; Flow Cytometry; Funding; Generations; Genes; Genetic; Gleevec; Goals; Growth; Guidelines; Hematopoietic Neoplasms; Housekeeping Gene; Immune response; Individual; Infection; Laboratories; Leukocytes; Liquid substance; Malignant Neoplasms; Messenger RNA; Names; National Cancer Institute; Numbers; Outcome; Pathway interactions; Patients; Personal Satisfaction; Persons; Pharmaceutical Preparations; Phase; Phase I Clinical Trials; Phycoerythrin; Physicians; Polymerase Chain Reaction; Population; Preparation; Process; Production; Quality Control; RNA; Reaction; Reporter; Reporting; Research; Resistance; Risk; Sampling; Serological; Signal Transduction; Stratification; Streptavidin; Subgroup; System; Technology; Testing; Therapeutic; Thinking; Training; Transcript; Tube; Validation; assay development; austin; base; clinically relevant; clinically significant; cost; design; drug development; experience; fluorophore; instrument; leukemia; multiplex detection; novel therapeutics; nuclease; rapid detection; research clinical testing; size; solution hybridization; success; therapeutic target; young adult

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.

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细胞生长不受控制。癌细胞的积累会干扰人体健康血细胞的产生，从而损害对感染的免疫反应。在全世界范围内，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。据美国癌​​症协会称，2003 年美国报告了 30,800 例各种类型白血病的新病例。白血病是 20 岁以下儿童和年轻人癌症死亡的第一大原因。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母细胞内的特定染色体易位，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生和进展，因此是治疗靶点和诊断标记物。新的治疗方法可能会进一步提高识别特定白血病相关易位的重要性，以确定最有效的治疗方案。具有流式细胞术检测功能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分析的基础。这种格式通常应用于临床分析，包括血清学、遗传和传染病目标。该项目的第一阶段资金支持成功开发快速单管测定法，使用融合转录本作为标记（21 个融合转录本标记）同时检测白血病相关染色体易位。第一阶段研究还表明了用于临床实施该测定的综合控制系统的可行性。因此，我们推出了一款试剂盒（仅供研究使用，RUO），用于快速检测来自最常见白血病相关易位的 12 种融合转录标记物，商品名为 Signature LTx Leukemia Translocation Panel。拟议的第二阶段项目的最终目标是将该检测方法改编并扩展为强大的高通量临床诊断试剂盒，用于白血病的快速风险分层。 II 期的具体目标是： 1. 扩大检测范围以包括其他临床相关标记。 2. 开发用于该测定的临床测试的综合测定控制系统。 3. 我们的快速白血病亚型分析系统的临床评估（风险分层）。该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方法（Signature LTx）。该测定的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重要信息。