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: 3174049
• 负责人: Joseph R. Testa
• 金额: $ 8.86万
• 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/3174049
• 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 来自一大批急性白血病患者。一份诊断报告， 每名患者治疗前的骨髓样本将进行三次检查 不同的高分辨率技术。细长的，细密的带子 用新的程序获得的染色体可以更精确地 异常的识别。详细的核子学研究将 与对其结构和表达的研究相结合 这些患者白血病细胞中的各种癌基因。我们计划 在一大系列的基础上进一步评估，无论大多数 急性白血病患者是否存在克隆性染色体缺陷 微妙的重新安排经常发生。带得很细的染色体会 用于更准确地识别断点。调查将会进行 确定高分辨率显带分析是否可以揭示新的亚群 以一致、细微的染色体变化为特征的患者 具有鲜明的临床病理特征。这些发现将是重要的 在识别可能携带对正常细胞至关重要的基因的染色体位置 控制特定靶细胞的增殖和分化。一 长期目标是将染色体缺陷与染色体的变化联系起来 受影响断裂点的基因功能和调控。作为首字母 我们将尝试将特定的染色体变化与 特定癌基因的结构和转录的改变。一个 细胞库将被开发为未来白血病细胞的来源 学习。另一个长期目标是找到可靠的预测 指标。最近的证据表明，用不同的方法获得的结果 细胞遗传学方法可能没有可比性。将会有大量的细胞 对每个病人进行仔细检查，这将使 定量比较三种不同的高分辨率技术与 关于：(A)个体内异常有丝分裂的比例 样本；及。(二)在 病人群体。核型模式将与 治疗反应和存活率确定哪种高分辨率方法 或多种方法联合应用可提供最准确的预后指标。 (K)