Biospecimens

核心1摘要 鉴于发生里希特病的慢性淋巴细胞白血病(CLL)患者预后较差 综合征(RS)，扩大对RS的分子理解对于理解 患者面临的风险最大，并需要制定改进的治疗策略。目前没有 为RS患者提供有效的护理治疗标准，这可能是一个日益严重的问题，因为 越来越多的接受新药治疗的慢性淋巴细胞性白血病患者寿命延长，使他们面临 发展RS。Core 1的基本任务是确保临床上有强大的组织资源 对RS患者的原始样本进行注释，在临床试验和非临床试验中进行治疗。此外，我们 将最大限度地获得匹配的CLL样本-非常可行，因为我们的长期- 建立了深度CLL样本库--使RS和先前CLL之间的克隆关系， 以及这两个相关实体之间的分子和功能差异，可以进行研究。我们会 此外，我们还将继续对所有CLL患者的细胞和血浆样本进行系统存储 中间。我们将强调，在任何证据表明之前，我们都将重点关注那些患有RS的高风险人群。 转化，同时他们的CLL已经进展到RS，用于评估无细胞DNA作为一种 早期发现的方法。以这种方式，此核心的资源将为项目提供 必要的原代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，以获得 来自参加治疗试验的患者和试验外治疗的患者的新鲜RS活检 布景。我们有完善的系统来有效地分配细胞和核酸材料 在整个计划中，用于项目中描述的深度分子分析。我们还有更多 与外部临床试验地点协调，共享处理SOP，以便活检材料可以 在不同的研究和机构中以统一的方式获得和处理。我们已经有足够的 我们的生物库中的RS患者样本，使我们能够立即开始通过 项目。通过本核心部分详细介绍的努力，我们计划大幅增加 在本奖项的整个时间线内提供此类样品以推动项目的科学性，以及 更远一点。这些努力将为今后将研究成果转化为 RS发展的潜在新生物标志物以及RS本身的生物学及其潜力 治疗的脆弱性，从而促进新的临床试验的发展。

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.