BIOSPECIMENS AND XENOGRAFT

摘要 Core 2的主要目标是为SPORE提供所需的基础设施和专业知识 储存、表征和分发原代标本和患者源性异种移植（PDX）模型。这些 将通过管理人员制定的既定方案从患者中前瞻性收集 核心（核心1），通过翻译核心（核心3）使用新型分子生物标志物检测进行测定，并作为 每个研究项目的基本试剂。核心2将由杰罗姆里兹博士和 博士大卫温斯托克。杰罗姆里兹博士在DFCI从事白血病和移植研究超过10年。 30年，在细胞采集、处理、冻存、流式细胞仪分析方面有丰富的经验 和纯化，移植免疫学和数据库开发。Ritz博士目前是执行官 DFCI的Connell O'Reilly细胞操作核心设施（CMCF）主任。Pasquarello组织库 2001年成立了血液肿瘤科，作为CMCF的一个单位，将负责 为该孢子加工、储存和分销原发性骨髓恶性肿瘤。此资源 已经从1,500多名独特的髓性白血病患者中采集了4,000多份骨髓样本， 可供SPORE调查人员使用。Weinstock博士指导DFCI血液学检查 PDX存储库，其中已经包含超过300个可移植的PDX模型，这些模型已经过可行的冷冻保存 并可供SPORE调查人员使用。这些通过全转录组测序完全表征， DNA测序、免疫分型和其他分子分析。现有患者样本和PDX生产线 已与项目调查人员共享。此外，核心具有丰富的经验， 利用原代患者样本进行体外测定，并利用PDX模型进行体内新化合物的临床前试验， 治疗核心的目的1是从入组的骨髓恶性肿瘤患者中采集原始样本， 临床研究方案以及分离和保存活的单核细胞、DNA和血浆。目标二是 建立、表征和分发骨髓恶性肿瘤异种移植物模型并促进临床前试验 与项目合作。目标3是维护包含病理学、细胞遗传学和遗传学的注释数据库， 从髓系白血病患者获得的临床样品和异种移植物的分子信息 恶性肿瘤。通过成功地实现这些目标，核心在联合国的成功中发挥着至关重要的作用。 SPORE及其集体努力，以改善骨髓肿瘤患者的诊断和治疗。

Abstract The major goals of Core 2 are to provide the SPORE with the infrastructure and professional expertise needed to bank, characterize and distribute primary specimens and patient-derived xenograft (PDX) models. These will be prospectively collected from patients through established protocols developed by the Administrative Core (Core 1), assayed using novel molecular biomarker tests by the Translational Core (Core 3) and serve as essential reagents for each of the Research Projects. Core 2 will be jointly directed by Drs. Jerome Ritz and Dr. David Weinstock. Dr. Jerome Ritz has worked in leukemia and transplant research at DFCI for more than 30 years and has extensive experience in cell collection, processing, cryopreservation, flow cytometric analysis and purification, transplant immunology, and database development. Dr. Ritz is currently the Executive Director of the Connell O'Reilly Cell Manipulation Core Facility (CMCF) at DFCI. The Pasquarello Tissue Bank for Hematologic Malignancies was established as a unit of the CMCF in 2001 and will be responsible for processing, banking and distribution of primary myeloid malignancies for this SPORE. This resource has already acquired over 4,000 bone marrow samples from over 1,500 unique patients with myeloid leukemias that are available for use by SPORE investigators. Dr. Weinstock directs the DFCI Hematologic Malignancy PDX repository, which already contains >300 transplantable PDX models that have been viably cryopreserved and are available for SPORE investigators. These are fully characterized by whole transcriptome sequencing, DNA sequencing, immunophenotyping and other molecular assays. Existing patient samples and PDX lines have already been shared with Project investigators. Moreover, the Core has extensive experience with utilizing primary patient specimens for in vitro assays and PDX models for in vivo pre-clinical trials of novel therapies. Aim 1 of the Core is to acquire primary samples from patients with myeloid malignancies enrolled in clinical research protocols and to isolate and preserve viable mononuclear cells, DNA and plasma. Aim 2 is to establish, characterize, and distribute xenograft models of myeloid malignancies and facilitate pre-clinical trials in collaboration with the Projects. Aim 3 is to maintain annotated databases containing pathologic, cytogenetic and molecular information for clinical samples and xenografts obtained from patients with myeloid malignancies. By successfully pursuing these aims, the Core plays an essential role in the success of the SPORE and its collective efforts to improve the diagnosis and treatment of patients with myeloid neoplasms.