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（由申请人提供）：急性淋巴细胞白血病（ALL）是 在临床结局中表现出异质性的疾病。 其中一些 异质性反映出存在独特的非随机染色体 易位，与不同的临床结局有关。 许多 这些染色体易位导致新型融合基因。 我们假设 这些融合的基因诱导了异常的基因表达模式，并且 是这些易位有助于发展的机制 白血病，因此会影响预后。 但是，并非所有人 临床结果的异质性可以通过易位来解释。 我们 假设所有人的其他特定异质特征，例如 对化学治疗剂的可变反应也反映在不同的 基因表达的模式。 本提案中描述的项目的广泛目标是使用 大量基因的表达水平的测量 更好地了解所有人的特定特征。 为了使 这样的测量值，我们将利用最近开发的高密度cDNA 微阵列技术。 该项目的具体目的是：（1）确定不同的模式 与特定染色体相关的基因表达 t r anslosation，（2）识别基因表达的不同模式 与化学疗法的敏感性或抗性相关，（3）使用基因 表达测量值以识别重要的诊断和预后 所有以前尚未被认可的亚型，以及（4）开发 所有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 对所有人的理解。 首先，我们将对 分子机制负责所有人的发展。 第二，我们会的 深入了解所有人的化学疗法耐药性机制，从而 促进开发克服这种抗性的方法。 第三， 通过鉴定所有人的先前未认可的亚型，我们 期望促进新颖，临床上有用的标记的发展 指导这种疾病。 第四，通过利用新颖的建模 技术，我们希望对基因转录有更深入的了解 所有重要的网络。