Large deletions at the t(9;22) breakpoint are common and may identify a poor-prognosis subgroup of patients with chronic myeloid leukemia
Large deletions at the t(9;22) breakpoint are common and may identify a poor-prognosis subgroup of patients with chronic myeloid leukemia
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DOI：
10.1182/blood.v95.3.738.003k21_738_743
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发表时间：
2000-02-01
期刊：
影响因子：
20.3
通讯作者：
Green, AR
中科院分区：
文献类型：
--
作者：
Sinclair, PB;Nacheva, EP;Green, AR
慢性髓性白血病（CML）的标志是BCR-ABL融合基因，该基因通常是由t(9；22)易位，CML患者在其临床表现和进化到爆发危机所需的时间上都表现出相当大的异质性，在本研究中，中期荧光原位杂交显示，相当少数的CML患者在衍生染色体9的易位断点附近，在变异易位的额外伴侣染色体上，或在两者上都有大的缺失。缺失跨越了几个大碱基，具有可变的断点，并且可以在未分离的骨髓和纯化的外周血粒细胞中通过微卫星聚合酶链反应检测到。缺失可能发生在费城（Ph）染色体易位的早期和可能发生的时候：在11例患者的诊断中检测到缺失，在所有Ph阳性中期都发现，并且在Ph染色体变异的患者中更为普遍。Kaplan-Meier分析显示，缺失患者的中位生存时间为36个月；没有检测到缺失的患者存活了90个月。多因素分析表明，缺失状态对预后的重要性与年龄、性别、外周血原细胞百分比和血小板计数无关。因此，我们的数据表明，一个表面上简单、平衡的易位不仅可能导致一个显性融合癌基因的产生，还可能导致一个或多个影响疾病进展的基因的丢失。(C) 2000年由美国血液学会出版。
The hallmark of chronic myeloid leukemia (CML) Is the BCR-ABL fusion gene, which is usually formed as a result of the t(9;22) translocation, Patients with CML show considerable heterogeneity both in their presenting clinical features and in the time taken for evolution to blast crisis, in this study, metaphase fluorescence in situ hybridization showed that a substantial minority of patients with CML had large deletions adjacent to the translocation breakpoint on the derivative 9 chromosome, on the additional partner chromosome in variant translocations, or on both. The deletions spanned up to several mega-bases, had variable breakpoints, and could be detected by microsatellite polymerase chain reaction in unfractionated bone marrow and purified peripheral blood granulocytes, The deletions were likely to occur early and possibly at the time of the Philadelphia (Ph) chromosome translocation: deletions were detected at diagnosis in 11 patients, were found in all ph-positive metaphases, and were more prevalent in patients with variant Ph chromosomes. Kaplan-Meier analysis showed a median survival time of 36 months in patients with a deletion; patients without a detectable deletion survived > 90 months. The survival-time difference was significant on log-rank analysis (P = .006), Multivariate analysis demonstrated that the prognostic importance of deletion status was independent of age, sex, percentage of peripheral blood blasts, and platelet count. Our data therefore suggest that an apparently simple, balanced translocation may result not only In the generation of a dominantly acting fusion oncogene but also in the loss of one or more genes that influence disease progression.(C) 2000 by The American Society of Hematology.