Biospecimens

核心1摘要 考虑到患有慢性淋巴细胞白血病（CLL）的患者预后不良， 综合征（RS），扩展RS的分子理解是至关重要的，无论是了解 患者面临的风险最大，因此需要开发更好的治疗策略。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， 越来越多的CLL患者用新的药物治疗寿命更长，使他们面临风险， 发展RS。核心1的基本使命是确保临床- 来自在临床试验期间和临床试验结束时接受治疗的RS患者的注释原始样本。另外我们 将最大限度地利用机会获得匹配的CLL样本-高度可行，因为我们长期- 建立了深层CLL样本库， 以及这两种相关实体之间的分子和功能差异。我们将 我还继续我们的细胞和血浆样本的系统银行从所有CLL患者看到我们的 中心我们将强调银行那些高风险的发展RS，无论是在任何证据之前， 转化，并且在他们的CLL已经进展到RS的时候，用于评估游离DNA作为一种细胞因子。 早期检测方法。以这种方式，该核心的资源将为项目提供 必要的主要RS和CLL组织，以了解起源，生物学，和最有前途的 RS中的治疗靶点。我们已经建立了基础设施和协调的工作流程， 新鲜RS活检标本，来自治疗试验入组患者和试验外接受治疗的患者 设置.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，如项目中所述，进行深度分子分析。我们进一步 与外部临床试验中心协调，共享处理SOP，以便可以 以统一的方式在研究和机构中获得和处理。我们已经有足够的 我们的BioBanks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述的努力，我们计划大幅提高 在本奖项的整个时间轴内，这些样本的可用性为项目的科学提供了动力， 超越。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 治疗的弱点，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.