Gene Expression Patterns in Acute Lymphoblastic Leukemia

急性淋巴细胞白血病的基因表达模式

• 批准号: 6464706
• 负责人: BERNARD M FINE
• 金额: $ 13.26万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6464706
• 关键词: acute lymphocytic leukemia; antineoplastics; asparaginase; cell line; chromosome translocation; clinical research; complementary DNA; cytogenetics; daunorubicin; drug resistance; gene expression; genetic models; genetic transcription; human tissue; microarray technology; model design /development; molecular oncology; neoplasm /cancer chemotherapy; neoplasm /cancer classification /staging; neoplasm /cancer genetics; pharmacogenetics; prednisolone; vincristine

DESCRIPTION (provided by applicant): Acute lymphoblastic leukemia (ALL) is a disease that exhibits heterogeneity in clinical outcome. Some of this heterogeneity is reflected by the presence of distinct nonrandom chromosomal translocations, which are associated with distinct clinical outcomes. Many of these chromosomal translocations result in novel fused genes. We hypothesize that these fused genes induce aberrant gene expression patterns and that this is the mechanism by which these translocations contribute to the development of leukemia and, consequently, affect prognosis. However, not all of the heterogeneity in clinical outcome can be explained by translocations. We hypothesize that other specific heterogeneous features of ALL, such as variable response to chemotherapeutic agents, are also reflected in distinct patterns of gene expression. The broad goals of the project described in this proposal are to use measurements of the expression levels of a large number of genes in ALL to gain a better understanding of specific features of ALL. In order to make such measurements, we will exploit recently developed high-density cDNA microarray technology. The specific aims of this project are: (1) to identify distinct patterns of gene expression that are associated with particular chromosomal t r anslocations, (2) to identify distinct patterns of gene expression associated with sensitivity or resistance to chemotherapy, (3) to use gene expression measurements to identify important diagnostic and prognostic subtypes of ALL, that have not previously been recognized, and (4) to develop testable models for the gene transcription pathways involved in ALL. Through this work, we expect to make a number of important contributions to the understanding of ALL. First, we will gain a deeper understanding of the molecular mechanisms responsible for the development of ALL. Second, we will gain insight into the mechanisms of chemotherapy resistance in ALL and, thus, facilitate the development of methods to overcome this resistance. Third, through the identification of previously unrecognized subtypes of ALL, we expect to facilitate the development of novel, clinically useful markers to guide treatment in this disease. Fourth, by exploiting novel modeling techniques, we expect to gain a deeper understanding of the gene transcription networks that are important in ALL.

描述(申请人提供)：急性淋巴细胞白血病(ALL)是一种 在临床结果上表现出异质性的疾病。这其中的一些 异质性反映在不同的非随机染色体的存在上。 易位，这与不同的临床结果有关。许多. 这些染色体易位导致了新的融合基因。我们假设 这些融合基因诱导了异常的基因表达模式，这 是这些易位促进发育的机制 白血病的风险，从而影响预后。然而，并非所有的 临床结果的异质性可以用易位来解释。我们 假设所有的其他特定的异类特征，例如 对化疗药物的不同反应也反映在不同的 基因表达模式。 本建议书中描述的项目的总体目标是使用 ALT中大量基因表达水平的测量 更好地了解所有人的具体特征。为了使 这样的测量，我们将利用最近开发的高密度cdna 微阵列技术。 该项目的具体目标是：(1)确定不同的模式 与特定染色体相关的基因表达 易位，(2)识别不同的基因表达模式 与化疗敏感或耐药有关，(3)使用基因 表达测量以确定重要的诊断和预后 ALL的亚型，以前没有被认识到的，以及(4)发展 ALL中涉及的基因转录途径的可测试模型。 通过这项工作，我们希望为以下方面做出一些重要贡献 所有人的理解。首先，我们将更深入地了解 ALL发生的分子机制。第二，我们将 了解ALL中化疗耐药的机制，从而， 促进制定克服这种阻力的方法。第三, 通过识别以前未识别的ALL亚型，我们 期望促进新的、临床上有用的标记的开发 指导这种疾病的治疗。第四，通过开发新颖的建模 技术，我们希望对基因转录有更深的理解。 对所有人都很重要的网络。