DETECTION OF SOMATIC GENE MUTATIONS IN HEMATOLOGIC DISEASES

血液疾病中体细胞基因突变的检测

• 批准号: 2571441
• 负责人: S ROSENFELD
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2571441
• 关键词: CD2 molecule; clinical research; dyserythropoietic anemia; fibroblasts; fusion gene; gene mutation; human subject; interview; myelogenous leukemia; neoplasm /cancer genetics; retinoid binding proteins; tissue /cell culture

A number of hematologic diseases have been shown to result from clonal expansion of an abnormal stem cell. In a few cases, typically associated with macroscopic chromosomal structural abnormalities, individual genes have been implicated. Examples include chronic myelogenous leukemia (CML) and the BCR-Abl fusion gene, and acute promyelocytic leukemia (APL) and the retinoic acid receptor. Detection of a specific genetic abnormality has had a significant impact on the diagnosis and treatment of CML and APL. No specific or consistent genetic abnormality has been detected in the majority of clonal bone marrow disorders, including the myelodysplastic syndromes and the myeloproliferative syndromes other than CML. We are in the process of implementing representational difference analysis to look for changes in the somatic DNA of individuals with clonal bone marrow disorders. We have had promising results with our test samples. If these results are confirmed, we will proceed with the analysis of previously collected patient samples, using DNA collected from autologous cultured skin fibroblasts as a source of normal DNA and DNA collected from peripheral blood as a source of abnormal DNA.

已证明许多血液系统疾病是由 异常干细胞的克隆扩增。在少数情况下，通常 与宏观染色体结构异常相关， 个别基因受到牵连。例子包括慢性 骨髓性白血病 (CML) 和 BCR-Abl 融合基因以及急性 早幼粒细胞白血病（APL）和视黄酸受体。 特定基因异常的检测具有重大意义 对CML和APL的诊断和治疗产生影响。没有具体或 大多数人都检测到了一致的遗传异常 克隆性骨髓疾病，包括骨髓增生异常 综合征和除 CML 之外的骨髓增殖综合征。 我们正在实施代表性差异 分析以寻找患有此病的个体体细胞DNA的变化 克隆性骨髓疾病。我们已经取得了有希望的结果 测试样品。如果这些结果得到证实，我们将继续 使用 DNA 分析之前收集的患者样本 从自体培养的皮肤成纤维细胞中收集作为来源 正常 DNA 和从外周血采集的 DNA 作为来源 异常DNA。