HIGH-RESOLUTION CHROMOSOME ANALYSIS OF ACUTE LEUKEMIA

急性白血病的高分辨率染色体分析

• 批准号: 3174048
• 负责人: Joseph R. Testa
• 金额: $ 8.46万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-01-01 至 1987-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3174048
• 关键词: chromosome disorders; clone cells; cytogenetics; genetic mapping; human subject; lymphocytic leukemia; neoplasm /cancer genetics; oncogenes

We will perform high-resolution chromosome analysis on bone marrow cells from a large series of patients with acute leukemia. A diagnostic, pre-treatment marrow specimen on each patient will be examined with three different high-resolution techniques. The elongated, finely banded chromosomes obtained with the newer procedures allow more precise identification of abnormalities. Detailed karyologic investigations will be done in conjunction with studies on the strucure and expression of various oncogenes in leukemic cells from these patients. We plan to further assess, on the basis of a large series, whether or not most patients with acute leukemia have clonal chromosome defects and whether subtle rearrangements frequently occur. The finely banded chromosomes will be used to identify breakpoints more precisely. The investigation will determine if high-resolution banding analysis can reveal new subgroups of patients characterized by a consistent, subtle chromosome change and distinctive clinicopathologic features. These findings will be important in identifying chromosome sites that may carry genes critical to the normal control of proliferation and differentiation of specific target cells. One long-term objective is to relate chromosome defects to changes in the function and regulation of genes at affected breakpoints. As an initial step we will attempt to associate specific chromosome changes with alterations in the structure and transcription of specific oncogenes. A cell bank will be developed as a source of leukemic cells for future study. Another long-term objective is to find reliable prognostic indicators. Recent evidence suggests that results obtained with different cytogenetic methods may not be comparable. A large number of cells will be carefully examined from each patient which will make it feasible to quantitatively compare the three different high-resolution techniques with respect to: (a) the proportion of abnormal mitoses within individual specimens; and (b) the overall rate of detection of abnormal clones in the patient population. The karyotypic pattern will be correlated with therapeutic response and survival to determine which high-resolution method or combination of methods gives the most accurate indication of prognosis. (K)

我们将对骨髓细胞进行高分辨率染色体分析 急性白血病患者的研究。 一个诊断， 每例患者的治疗前骨髓标本将用三种 不同的高分辨率技术。 细长的，细带状的 用新的方法获得的染色体可以更精确地 识别异常。 详细的细胞核学研究将 结合对结构和表达的研究， 这些患者白血病细胞中的各种癌基因。 我们计划 在一个大系列的基础上进一步评估， 急性白血病患者有克隆性染色体缺陷， 经常发生细微的重排。 精细的染色体将 用于更精确地识别断点。 调查将 确定高分辨率条带分析是否可以揭示新的亚组 患者的特点是一致的，微妙的染色体变化， 独特的临床病理特征。 这些发现将是重要的 在确定染色体位点，可能携带基因的关键正常 控制特定靶细胞的增殖和分化。 一 长期的目标是将染色体缺陷与 在受影响的断点基因的功能和调节。 作为初始 我们将尝试将特定的染色体变化与 特定致癌基因的结构和转录的改变。 一 细胞库将被开发为未来白血病细胞的来源 study. 另一个长期目标是找到可靠的预后指标。 指标 最近的证据表明，用不同方法获得的结果 细胞遗传学方法可能无法比较。 大量的细胞将 仔细检查每一个病人，这将使它可行， 定量比较三种不同的高分辨率技术， （a）个体内异常有丝分裂的比例 （B）样本中异常克隆的总检出率 患者人群。 核型模式将与 治疗反应和生存率，以确定哪种高分辨率方法 或方法的组合给出最准确的预后指示。 （K）