TRANSFORMATION BY BCR-ABL ONCOGENES

BCR-ABL 癌基因的转化

基本信息

批准号：
2094616
负责人：
STEVEN S CLARK
金额：
$ 8.79万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
1991
资助国家：
美国
起止时间：
1991-07-01 至 1996-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2094616
关键词：
Abelson leukemia virus B lymphocyte Retroviridae T lymphocyte cell differentiation cell growth regulation disease vectors genetic transcription hematopoietic stem cells laboratory mouse leukocyte activation /transformation lymphocyte mutant neoplastic transformation oncogenes transforming virus viral carcinogenesis

项目摘要

Our major research goal is to understand the mechanisms used to control differentiation and lineage commitment of normal hematopoietic cells, and how these processes are affected by neoplastic transformation. Our efforts focus on the human P210 and P185 bcr-abl oncogenes that are expressed from the philadelphia chromosome (Ph) translocation and their interactions with hematolymphoid progenitor cells. Evidence from the pathogenesis of human Ph+ leukemia suggests that bcr-abl oncogenes can regulate the growth of primitive hematopoietic stem cells that maintain the ability to full differentiate. this raises the possibility that the genes may be used experimentally to stimulate the growth of progenitor populations capable of differentiating along different pathways. such a system would be useful for determining the developmental potential of selected precursor cells and for examining the regulation of hematopoietic differentiation from a developmentally synchronized precursor population. These studies will use retroviral vectors that express bcr-abl to test the interaction of the genes on different hematolymphoid progenitor cells. Specifically we wish to 1. Determine the range and differentiation potential of bcr-abl transformation targets in the thymus, 2. Identify new lymphoid progenitors that can be transformed with the b r-abl viruses and characterize their differentiative potential, and 3. Compare the interaction of different bcr-abl oncogenes and engineered bcr-abl mutants on the differentiation of developmentally synchronized lymphocyte progenitors. This will serve as a model in which to test additional genes that may cooperate with bcr-abl in regulating cell growth vs differentiation. These experiments will contribute to our knowledge of the role of bcr-abl in human leukemias, and provide a way to study the earliest steps in the differentiation of lymphocyte progenitors into mature T and B cells.

我们的主要研究目标是了解用于控制的机制正常造血细胞的分化和谱系定型，以及这些过程如何受到肿瘤转化的影响。我们的努力重点关注人类 P210 和 P185 bcr-abl 癌基因，它们表达于费城染色体 (Ph) 易位及其与血淋巴祖细胞。来自人类发病机制的证据 Ph+白血病表明bcr-abl癌基因可以调节细胞的生长原始造血干细胞维持充分的能力区分。这增加了基因可能被使用的可能性通过实验刺激祖细胞群的生长沿着不同的路径进行差异化。这样的系统会有用用于确定选定前体细胞的发育潜力和用于检查造血分化的调节发育同步的前体种群。这些研究将使用表达 bcr-abl 的逆转录病毒载体来测试不同造血淋巴祖细胞上基因的相互作用。具体来说，我们希望 1. 确定范围和差异化胸腺中 bcr-abl 转化目标的潜力，2. 识别新的可以用 br-abl 病毒转化的淋巴祖细胞描述其差异化潜力，以及 3. 比较不同bcr-abl癌基因和工程bcr-abl突变体的相互作用发育同步淋巴细胞分化的研究祖先。这将作为测试其他基因的模型可能与 bcr-abl 合作调节细胞生长差异化。这些实验将有助于我们了解 bcr-abl 的作用人类白血病，并提供一种研究最早步骤的方法淋巴细胞祖细胞分化为成熟的 T 细胞和 B 细胞。