Animal Modeling and Clinical Resources Core

动物建模和临床资源核心

• 批准号: 8589113
• 负责人: David F Claxton
• 金额: $ 35.02万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-10 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8589113
• 关键词: Acute Myelocytic Leukemia; Aliquot; Animal Model; Cell Line; Clinical; Clinical Data; Clonal Evolution; Disease; Exhibits; Goals; Hematopoietic; Human; Metabolism; Modeling; Mus; Oncogenic; Outcome; Patients; Plasma Cells; Proteins; Resources; Role; Sampling; Sphingolipids; Technology; Testing; Therapeutic; Treatment outcome; Xenograft Model; Xenograft procedure; base; cell bank; design; efficacy testing; leukemia; leukemogenesis; novel; programs; repository; therapy development

Human acute myelogenous leukemia (AML) is highly heterogeneous and, as demonstrated by this group, exhibits significant variability in sphingoiipid metabolism. Current therapy of AML is highly toxic, yielding ultimately inadequate outcomes for the vast majority of patients. Cell lines are limited in their representation of primary AML subtypes and manifest clonal evolution in culture, suggesting limitations in their relationship to the primary case hnaterial. The systematic study of these diseases thus requires access to primary samples representing a substantial pool of cases, and correlation of these samples to clinical data including treatment outcomes. Animal models of various kinds are available, but models representing direct leukemogenesis via expression of relevant oncogenic proteins and immunodeficient xenografts propagating primary AML, provide relevant platforms for studying developing therapies. In this Core, materials and models will be provided to each Project to allow completion of proposed objectives. The following specific aims will be pursued: Specific Aim 1: Expand and maintain the PSHCI leukemia cell bank to provide programmatic access to cell and plasma samples from a broad variety of AML patients and normal hematopoietic controls. Samples will be cryopreserved in multiple aliquots to allow repeated interrogation via developing technologies. Clinical data will be collected and available to provide biologically meaningful categorization of AMLs. Specific Aim 2: Develop and maintain a menu of animal models in which to test promising program-derived therapies. Two such models are available. Subaim 2A: Xenograft models of primary human leukemia have been developed in N0D/SCID/IL2rY

人类急性髓系白血病(AML)是高度异质性的，正如这个小组所证明的那样， 狮身人面像的新陈代谢表现出显著的变异性。目前对急性髓细胞白血病的治疗是剧毒的，有效的 对于绝大多数患者来说，最终的结果是不充分的。细胞系在其代表性方面是有限的 原发AML亚型和培养中明显的克隆性进化，表明它们之间的关系存在局限性 与第一个案件有关。因此，对这些疾病的系统研究需要获得初级 代表大量病例的样本，以及这些样本与临床数据的相关性，包括 治疗结果。有各种各样的动物模型可用，但模型代表直接 相关癌基因蛋白的表达与免疫缺陷异种移植瘤的发生 原发AML，为研究开发疗法提供相关平台。在这个核心中，材料和 将向每个项目提供模型，以便完成拟议的目标。以下是具体的 将追求的目标：具体目标1：扩大和维护PSHCI白血病细胞库，以提供 程序化获取各种AML患者和正常人群的细胞和血浆样本 造血控制组。样品将在多份等份中超低温保存，以允许重复询问 通过开发技术。临床数据将被收集并可用来提供具有生物学意义的 AML的分类。具体目标2：开发和维护可用于测试的动物模型菜单 前景看好的程序化疗法。有两种这样的型号可供选择。Subaim 2A异种移植模型的建立 N0D/SCID/IL2rY已发展为原发人类白血病