Animal Modeling and Clinical Resources Core

人类急性髓细胞性白血病（AML）是高度异质性的，正如该组所证明的， 在鞘脂代谢中表现出显著的可变性。目前的AML治疗是高毒性的， 对绝大多数患者来说，最终的结果是不充分的。细胞系的代表性有限 原发性AML亚型和文化中表现出的克隆进化，表明它们之间的关系存在局限性 与主要病例材料吻合因此，对这些疾病的系统研究需要获得初级保健服务。 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。各种动物模型都是可用的，但代表直接免疫的模型。 通过相关致癌蛋白表达和免疫缺陷异种移植物增殖的白血病发生 原发性AML，为研究开发治疗提供相关平台。在这个核心中，材料和 将为每个项目提供模型，以完成拟议目标。以下具体 具体目标1：扩大和维持PSHCI白血病细胞库， 可编程访问来自各种AML患者和正常人的细胞和血浆样本 造血控制样本将以多个等分试样冷冻保存，以允许重复询问 通过发展技术。将收集临床数据，以提供生物学意义 AML的分类。具体目标2：开发和维护一份用于测试的动物模型菜单 有前途的程序衍生疗法有两种这样的模式。Subaim 2A： 原发性人类白血病已经在N 0 D/SCID/IL 2 rY中发展

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