Biospecimens and Primagraft Development

项目摘要 这个核心将提供一个无缝的翻译基础设施来支持CLL组织的研究 已在此应用程序中计划。这将包括提供新鲜或冷冻的初级CLL样品 (外周血、骨髓和淋巴结)，用于所有体外实验，并附有完整的临床注释 以及对已经登记在DFCI CLL组织库中的1200多名患者的随访 作为新入院的病人。核心包括从许多慢性淋巴细胞性白血病患者身上进行广泛的连续采样。 用新的药物治疗，并将特别关注进展和复发的获得 在这一授权期内的样品。这一核心还包括努力发展使用 原代CLL细胞建立体内原代移植模型。这些模型是一个重要的 越来越受欢迎的工具，用于分析新发现的遗传损伤、相关信号 以及生存途径、合理的治疗靶点和耐药机制。CLL细胞或 同基因细胞系将通过尾静脉注射或直接植入涂层支架内。 被运送到支架上的CLL细胞有望移植到这个“人性化的小鼠”系统中。 这是为了模拟CLL和BM细胞之间至关重要的人与人之间的异型相互作用。 这些原始模型可以用来表征生物学和评估对治疗的反应。 CLL的。这一核心最终也很容易提供转化为临床研究的机会 人体试验，因为我们的临床DFCI CLL计划由管理所有 临床研究试验和多中心研究的阶段。

Project Summary This core will provide a seamless translational infrastructure to support the research on CLL tissues planned in this application. This will include the provision of fresh or frozen primary CLL samples (peripheral blood, bone marrow and lymph node) for all in vitro experiments, with full clinical annotation and follow-up, from among the over 1200 patients already enrolled in the DFCI CLL tissue bank as well as newly enrolled patients. The core includes extensive serial sampling from many CLL patients treated with novel agents, and will focus particularly on the acquisition of progression and relapsed samples during this grant period. This core also includes an effort to develop the capability of using primary CLL cells to generate in vivo primagraft models. These models are a significant and increasingly appreciated tool for the analysis of newly identified genetic lesions, associated signaling and survival pathways, rational therapeutic targets and mechanisms of drug resistance. CLL cells or isogenic cell lines will be delivered by tail vein injection or directly implanted within the coated scaffolds. CLL cells delivered to the scaffolds are expected to engraft within this “humanized mouse” system which is meant to simulate vital human-human heterotypic interactions between CLL and BM cells. These primagraft models could then be used to characterize biology and assess response to therapy of the CLLs. This core ultimately also readily provides the opportunity for translation to clinical research trials in humans, as our clinical DFCI CLL program consists of recognized leaders in managing all phases of clinical research trials as well as multicenter studies.