UCCRC--ETIOLOGY OF TREATMENT-INDUCED SECONDARY LEUKEMIA

这个合作项目提出了一个研究的分子遗传 导致骨髓增生异常和/或白血病出现的机制， 既往接受过放疗和/或化疗的患者。 该计划开始时观察到，几乎90%的患者 继发于治疗的急性髓性白血病（t-AML）有缺失或缺失 5号或7号染色体上 过去五年的研究结果表明， 对t-AML病因学提出更具体的假设。 我们 建议：a）提供一个分子细胞遗传学分析， 恶性骨髓疾病中染色体5和7的异常; B）至 鉴定和克隆推定白血病抑制基因或抗白血病基因 (ALG)假设存在于5号染色体上; c）确定 涉及染色体11 q23带的易位断裂点的定位 相对于t-AML患者中拓扑异构酶结合位点的位置， d）确定表鬼臼毒素的作用， EGR 1是一个早期生长反应基因，定位于 5号染色体，在髓样分化和肿瘤发生中。 的项目 通过使用一组共同的患者和 将不同项目产生的数据综合成一个整体， 图中显示的是接受治疗的癌症患者的细胞变化。 期望这可能会导致对起源的理解 治疗相关的白血病 整个项目从治疗前到治疗期间对患者进行跟踪 和后续行动，并最终发展的第二次血液学 恶性肿瘤，因此可以提供致癌作用的一般描述 在人类身上。

This cooperative project proposes a study of the molecular genetic mechanisms leading to the appearance of myelodysplasia and/or leukemia in a group of patients previously treated with radiation and/or chemotherapy. The program started with the observation that almost 90% of patients with acute myeloid leukemia secondary to therapy (t-AML) had losses or deletions of chromosome 5 or 7. The studies of the past five years have resulted in the development of more specific hypotheses on the etiology of t-AML. We propose: a) to provide a molecular-cytogenetic analysis of the abnormalities of chromosomes 5 and 7 in malignant myeloid disorders; b) to identify and clone a putative leukemia suppressor or antileukemia gene (ALG) hypothesized to be present on chromosome 5; c) to determine the location of the translocation breakpoints involving chromosome band 11q23 relative to the location of topoisomerase binding sites in t-AML patients who have received epipodophyllotoxins; and d) to determine the role of EGR1, an early growth response gene, mapping to the critical region of chromosome 5, in myeloid differentiation and tumorigenesis. The projects are integrated by their use of a common set of patients and by the desire to synthesize the data generated by the different projects into an overall picture of the changes in the cells of treated cancer patients in the expectation that this may lead to an understanding of the origin of therapy-related leukemia. The overall project follows patients from pretreatment through treatment and follow-up and the ultimate development of a secondary hematologic malignancy and as such may provide a general description of carcinogenesis in humans.