UCCRC--ETIOLOGY OF TREATMENT-INDUCED SECONDARY LEUKEMIA

这个合作项目提出了一项关于分子遗传学的研究。 骨髓异常增生症和/或白血病的发生机制 一组以前接受过放射治疗和/或化疗的患者。 该计划一开始就观察到，近90%的患者患有 治疗后继发的急性髓系白血病(t-AML)有缺失或缺失 5号或7号染色体。过去五年的研究结果是 关于t-AML病因的更具体假说的发展。我们 建议：a)提供一种分子-细胞遗传学分析 恶性髓系疾病的5号和7号染色体异常； 鉴定和克隆一个可能的白血病抑制或抗白血病基因 (Alg)假设存在于5号染色体上；c)确定 涉及染色体11q23带的易位断裂点的定位 T-AML患者与拓扑异构酶结合部位的关系 已接受表鬼臼毒素的人；及d)确定 Egr1，一个早期生长反应基因，定位于 5号染色体，在髓系分化和肿瘤发生中。这些项目 是通过使用一组共同的病人和通过渴望 将不同项目生成的数据合成到一个整体 中国癌症治疗患者细胞变化情况图 期望这可能导致对…的起源的理解 与治疗相关的白血病。 整个项目跟踪患者从治疗到治疗的整个过程。 并随访并最终发展为继发性血液病 恶性，因此可以提供对癌症发生的一般描述 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.