Biospecimens

生物样本

• 批准号: 10270041
• 负责人: MATTHEW S DAVIDS
• 金额: $ 14.94万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10270041
• 关键词: Award; Biology; Biopsy; Bone Marrow; Bone marrow biopsy; Cells; Chronic Lymphocytic Leukemia; Clinical; Clinical Trials; Collection; Data; Development; Dissection; Doctor of Philosophy; Early Diagnosis; Enrollment; Ensure; Evaluation; Event; Foundations; Future; Genetic; Genome; Infrastructure; Institution; Methods; Mission; Molecular; Molecular Profiling; Mononuclear; Nucleic Acids; Pathogenesis; Patient-Focused Outcomes; Patients; Plasma; Process; Prognosis; Reporting; Resources; Richter' s Syndrome; Risk; Sampling; Science; Site; System; Therapeutic; Time; TimeLine; Tissues; Translational Research; biobank; cell free DNA; design; high risk; improved; improved outcome; lymph nodes; novel; novel marker; peripheral blood; phenome; programs; repository; sample collection; standard of care; therapeutic target; tissue resource; treatment trial

Core 1 Abstract Given the poor prognosis for patients with chronic lymphocytic leukemia (CLL) who develop Richter syndrome (RS), an expanded molecular understanding of RS is critical both to understand which patients are at greatest risk and to develop improved therapeutic strategies. There is currently no effective standard of care therapy for RS patients, and this is likely to be a growing problem, as increasing numbers of CLL patients treated with novel agents are living longer, putting them at risk of developing RS. The fundamental mission of Core 1 is to ensure a robust tissue resource of clinically- annotated primary samples from patients with RS treated both on and off clinical trials. Additionally, we will maximize opportunities to procure matched CLL samples—highly feasible because of our long- established deep CLL sample repository-- so that clonal relationships between RS and antecedent CLL, and molecular and functional differences between these two related entities, can be studied. We will also continue our systematic banking of cell and plasma samples from all CLL patients seen at our center. We will emphasize banking those at high risk for developing RS, both prior to any evidence of transformation and at the time their CLL has progressed to RS, for evaluation of cell-free DNA as a method of early detection. In this fashion, the resources of this Core will supply the Projects with the necessary primary RS and CLL tissue to understand the genesis, biology, and most promising therapeutic targets in RS. We have established the infrastructure and a coordinated workflow to obtain fresh RS biopsies both from patients enrolled on treatment trials and those treated outside the trial setting. We have well-established systems to efficiently distribute cellular and nucleic acid material across the Program, for deep molecular profiling as described in the Projects. We have further coordinated with external clinical trial sites to share processing SOPs so that biopsy material can be obtained and processed in a uniform fashion across studies and institutions. We already have sufficient RS patient samples in our BioBanks to allow us to immediately begin to generate data through the Projects. Through the efforts detailed in this Core section, we plan to significantly increase the availability of such samples to fuel the science of the Projects throughout the timeline of this award and beyond. These efforts will provide a firm foundation for future translation of the research findings into potential novel biomarkers of RS development, as well as the biology of RS itself and its potential therapeutic vulnerabilities, thereby facilitating the development of novel clinical trials.

核心1摘要 鉴于患有Richter的慢性淋巴细胞性白血病（CLL）患者的预后不良 综合征（RS），对RS的分子理解扩展对于了解哪种 患者面临最大的风险，并制定改进的治疗策略。目前没有 RS患者的有效护理疗法标准，这可能是一个日益严重的问题，因为 越来越多的新型药物治疗的CLL患者的寿命更长，使他们处于 开发卢比。核心1的基本任务是确保临床上强大的组织资源 带有RS患者的主要样品在临床试验内和关闭临床试验中进行了治疗。另外，我们 将最大化购买匹配的CLL样品的机会 - 非常可行 建立了深层CLL样品存储库 - 使得Rs和先前CLL之间的克隆关系， 这两个相关实体之间的分子和功能差异可以研究。我们将 还要继续我们从我们看到的所有CLL患者的细胞和血浆样品进行系统的库存 中心。我们将在任何证据之前都强调将卢比高风险的人存放 转化，当时它们的CLL已发展为RS，以评估无细胞DNA作为A 早期检测方法。以这种方式，该核心的资源将为项目提供 必要的初级RS和CLL组织，以了解起源，生物学和最有前途的 卢比的治疗靶标。我们已经建立了基础架构和协调的工作流程以获得 新鲜的RS活检均来自参加治疗试验的患者和试验外治疗的患者 环境。我们拥有良好的系统，可以有效地分布细胞和核酸材料 在整个程序中，如项目中所述进行深度分子分析。我们还有更多 与外部临床试验地点协调以共享处理SOP，以便活检材料可以是 在研究和机构之间以统一的方式获得和处理。我们已经有足够的 RS患者样本中的生物库中，使我们能够立即开始通过 项目。通过本核心部分中详细介绍的努力，我们计划显着增加 在本奖项的整个时间表中，此类样本的可用性为项目的科学推动了科学和 超过。这些努力将为将来的研究结果翻译成一个坚定的基础 RS开发的潜在新型生物标志物以及RS本身的生物学及其潜力 治疗脆弱性，从而支持新的临床试验的发展。