ETIOLOGY OF TREATMENT - INDUCED SECONDARY LEUKEMIA

这一合作项目提出了对分子机制的研究。 继发性急性非淋巴细胞白血病(ANLL)的出现 在一组以前接受过放射治疗和/或 化疗。几乎90%的ANLL患者继发于 心理治疗。建议：a)开发一系列多态DNA探针 位于染色体上持续缺失的关键区域 5和7；b)使用这些探针来定位更多的缺失区域 精确地在每个有5号或7号染色体缺失的患者中；c)测试 发育迟缓个体细胞的诱变敏感性 二次ANLL与适当对照的比较；d)确定水平 患者治疗前后细胞内06-甲基鸟嘌呤转移酶的变化 使用细胞毒性药物治疗，包括丙卡巴肼，它可能起到 甲基化试剂；及e)研究有利于基因融合的条件 以及由此产生的融合的结构。我们想知道的是 使用的治疗方法会产生新的基因关联。这些项目是一体化的 通过他们使用一组常见的患者，并试图将 在几个单独和合作项目中获得的数据转化为 年接受治疗的癌症患者细胞变化的总体情况 期望这可能导致对…的起源的理解 继发性恶性肿瘤。我们特别感兴趣的是知道 继发性白血病的出现是偶然发生的，还是一类 患者容易发生这样的事件。整个项目关注患者 从前期治疗到治疗和继发性发展 恶性，因此可以作为一种通用的癌变模型。 天哪。

This cooperative project proposes a study of the molecular mechanisms leading to the appearance of secondary acute nonlymphocytic leukemia (ANLL) in a group of patients previously treated with radiation and/or chemotherapy. It has almost 90 percent of patients with ANLL secondary to therapy. It is proposed to: a) Develop a series of polymorphic DNA probes located in the critical regions that are consistently deleted in chromosome 5 and 7; b) Use these probes to map the region of the deletion more precisely in each patient with a chromosome 5 or 7 deletion; c) Test the sensitivity to induced mutation of cells from individuals who develop secondary ANLL as compared to appropriate controls; d) Determine the level of 06-methylguanine transferase in cells of patients before and after treatment with cytotoxic agents, including procarbazine, which may act as methylating agents; and e) To study the conditions conducive to gene fusion and the structures of the resulting fusions. We wish to know how the treatments used induce new gene associations. The projects are integrated by their use of a common set of patients and by the attempt to correlate the data obtained in the several individual and cooperative projects into an overall picture of the changes in cells of treated cancer patients in the expectation that this may lead to an understanding of the origin of secondary malignancy. We are particularly interested in knowing whether the appearance of secondary leukemia occurs by chance or whether a class of patients is predisposed to such events. The overall project follows patients from pre-treatment through treatment and the development of secondary malignancy and as such may serve as a general model for carcinogenesis in man.