Genomic deletions on other chromosomes involved in variant t(9;22) chronic myeloid leukemia cases
Genomic deletions on other chromosomes involved in variant t(9;22) chronic myeloid leukemia cases
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DOI：
10.1002/gcc.10183
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发表时间：
2003-04-01
影响因子：
3.7
通讯作者：
Rocchi, M
中科院分区：
文献类型：
--
作者：
Albano, F;Specchia, G;Rocchi, M
费城（Ph）染色体是慢性粒细胞白血病（CML）的细胞遗传学标志，在超过90%的CML病例中观察到。在诊断时，5-10%的CML患者的Ph染色体来源于标准t（9;22）以外的变异易位。不同的研究小组最近描述了衍生9号染色体上邻近易位连接处的缺失。缺失可以鉴定具有更差预后的亚组。在CML变异易位患者中，除了9号和22号染色体外，其他三阶导数上是否存在类似的缺失还未被研究过。我们研究了三例慢性粒细胞白血病变异显示相对较大的缺失第三染色体参与易位。已知的肿瘤抑制基因（TSGs）或参与信号转导和细胞增殖调节的基因被发现位于这些缺失区域内。作为Knudson的两次打击模型的替代，“单倍不足”假说表明TSG的单个等位基因的缺失可以在肿瘤进展中起重要作用。我们的研究结果表明，应重视变异t（9;22）CML患者的分子细胞遗传学特征，以充分揭示CML的生物学异质性。(C)2003 Wiley-Liss，Inc.
The Philadelphia (Ph) chromosome is the cytogenetic hallmark of chronic myeloid leukemia (CML) and is observed in more than 90% of CML cases. At diagnosis, in 5-10% of CML patients the Ph chromosome is derived from variant translocations other than the standard t(9;22). Deletions adjacent to the translocation junction on the derivative chromosome 9 were recently described by different groups. The deletions may identify a subgroup with a worse prognosis. The presence of similar deletions on the third derivative other than the 9 and 22 chromosomes in CML with variant translocation has never been investigated. We studied three cases of CML variants showing relatively large deletions on the third chromosome involved in the translocation. Known tumor-suppressor genes (TSGs) or genes involved in signal transduction and in the modulation of cell proliferation were found to be located inside these deleted regions. As an alternative to Knudson's two-hit model, the "haplo-insufficiency" hypothesis suggests that the deletion of a single allele of a TSG can play an important role in tumor progression. Our findings suggest that great attention should be paid to the molecular cytogenetic characterization of variant t(9;22) CML patients to unveil fully the biological heterogeneity of CML. (C) 2003 Wiley-Liss, Inc.