Biospecimens

生物样本

• 批准号: 10491159
• 负责人: MATTHEW S DAVIDS
• 金额: $ 14.27万
• 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/10491159
• 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; patient prognosis; 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 鉴于患有里克特氏病的慢性淋巴细胞白血病 (CLL) 患者预后不良 综合征（RS），对 RS 的扩展分子理解对于理解哪种综合征至关重要 患者面临最大的风险并制定改进的治疗策略。目前没有 RS 患者的有效护理治疗标准，这可能是一个日益严重的问题，因为 越来越多接受新药治疗的 CLL 患者寿命更长，这使他们面临以下风险： 开发RS。核心 1 的基本使命是确保临床- 注释了来自临床试验内外接受治疗的 RS 患者的原始样本。此外，我们 将最大限度地增加获得匹配的 CLL 样本的机会——由于我们长期的 建立了深层CLL样本库——以便RS和先行CLL之间的克隆关系， 可以研究这两个相关实体之间的分子和功能差异。我们将 我们还继续系统地储存来自我们中心就诊的所有 CLL 患者的细胞和血浆样本 中心。我们将在出现任何证据之前，强调为那些患有 RS 的高风险人群提供银行服务。 转化，当时他们的 CLL 已进展为 RS，用于评估无细胞 DNA 作为 早期发现的方法。以这种方式，该核心的资源将为项目提供 必要的原发性 RS 和 CLL 组织，以了解起源、生物学和最有希望的 RS 的治疗靶点。我们已经建立了基础设施和协调的工作流程来获得 来自参加治疗试验的患者和试验外接受治疗的患者的新鲜 RS 活检 环境。我们拥有完善的系统来有效分配细胞和核酸材料 整个计划，用于项目中描述的深入分子分析。我们还有进一步 与外部临床试验中心协调共享处理 SOP，以便可以对活检材料进行处理 跨研究和机构以统一的方式获取和处理。我们已经有足够的 我们的生物库中存在 RS 患者样本，使我们能够立即开始通过 项目。通过本核心部分详述的努力，我们计划显着提高 提供此类样本，以推动整个奖项期间项目的科学性，以及 超过。这些努力将为今后将研究成果转化为成果奠定坚实的基础。 RS 发展的潜在新型生物标志物，以及 RS 本身的生物学及其潜力 治疗的弱点，从而促进新的临床试验的发展。