Quantitative HOX Expression as Prognostic Marker in AML

定量 HOX 表达作为 AML 的预后标志物

• 批准号: 6844440
• 负责人: HARRY A. DRABKIN
• 金额: $ 31.02万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-01-20 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6844440
• 关键词: acute myelogenous leukemia; analytical method; clinical research; cytogenetics; gene expression; genetic markers; homeobox genes; human genetic material tag; human tissue; method development; neoplasm /cancer genetics; polymerase chain reaction; prognosis

DESCRIPTION (provided by applicant): Homeodomain containing genes encode transcription factors that act during development to control pattern formation, differentiation and proliferation. Based on data from our laboratory and work of others, the quantitative analysis of HOX gene expression promises to be a powerful new tool in the prognostic assessment of patients with acute myelogenous leukemia (AML). To date, characteristic chromosomal alterations have been the gold standard for prognosis in AML. However, 50 percent of AML patients lack cytogenetic changes and another 10-20 percent have alterations considered to be of intermediate importance. Thus, a majority of patients with AML lack sufficient prognostic markers upon which definitive therapeutic decisions can be made. Our studies indicate that the patterns of quantitative HOX gene expression are in near total concordance with favorable and adverse chromosomal features. In addition, these expression patterns extend to the subset of patients with normal cytogenetics and other intermediate changes and are predictive of outcome. We propose to confirm and extend our initial observations on the importance of HOX gene expression in AML. In the R21, we will refine our quantitative assays to include the complete set of HOXA, HOXB and important TALE (PBX, MEIS) family members and validate the analytic performance of these assays. We will also explore the analysis of selected extended HOX and paraHox genes in AML for inclusion in the subsequent R33. The R33 phase will determine the role of quantitative HOX expression as a prognostic marker in AML, the association of HOX expression patterns with specific chromosomal features as well as resistant or relapsed disease, and should permit us to identify the most useful subset of HOX genes based on our analysis of large numbers of patients and disease phenotypes. Lastly, we will determine whether there is a relationship between HOX expression and another new predictor of outcome involving internal tandem duplications or mutations of the FLT3 receptor. Importantly, the HOX genes are more than markers of lineage, or differentiation. Rather, they are integrally involved in the pathogenesis of acute leukemia in both mice and man. Thus, their analysis provides insight into the disease process, and its heterogeneity, while providing new important prognostic information.

描述（由申请人提供）： 含有基因的同源域编码转录因子，在 开发以控制模式形成，分化和增殖。 根据我们的实验室和其他工作的数据，定量 HOX基因表达的分析有望成为强大的新工具 急性粒细胞性白血病（AML）患者的预后评估。到 日期，特征性染色体改变一直是金标准 AML的预后。但是，有50％的AML患者缺乏细胞遗传学变化 另外10-20％的变化被认为是中间的 重要性。因此，大多数AML患者缺乏足够的预后 可以做出确定的治疗决定的标记。我们的研究 表明定量HOX基因表达的模式在附近 总和有利和不良染色体特征。在 此外，这些表达模式扩展到患者的子集 正常的细胞遗传学和其他中间变化，并预测 结果。我们建议确认并扩展我们对 HOX基因表达在AML中的重要性。在R21中，我们将完善我们的 定量测定，包括完整的HOXA，HOXB和重要的测定 故事（PBX，MEIS）家庭成员并验证这些分析性能 测定。我们还将探索对选定的扩展HOX和Parahox的分析 AML中的基因包含在随后的R33中。 R33阶段将确定 定量HOX表达作为AML中预后标记的作用， HOX表达模式与特定染色体特征的关联 以及抗性或复发性疾病，应允许我们确定 根据我们对大量的分析，HOX基因最有用的子集 患者和疾病表型。最后，我们将确定是否有 HOX表达与结果的另一个新预测指标之间的关系 涉及FLT3受体的内部串联重复或突变。 重要的是，HOX基因不仅仅是谱系标记或 分化。相反，它们与 小鼠和人的急性白血病。因此，他们的分析提供了见识 进入疾病过程及其异质性，同时提供新的重要 预后信息。