Allelic loss determination in chronic lymphocytic leukemia by immunomagnetic bead sorting and microsatellite marker analysis
Allelic loss determination in chronic lymphocytic leukemia by immunomagnetic bead sorting and microsatellite marker analysis
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通过免疫磁珠分选和微卫星标记分析测定慢性淋巴细胞白血病的等位基因丢失
DOI：
10.1038/sj.onc.1200867
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发表时间：
1997
期刊：
影响因子：
8
通讯作者：
R. Gartenhaus
中科院分区：
文献类型：
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作者：
R. Gartenhaus
慢性淋巴细胞白血病(CLL)是西方世界最常见的成人白血病。目前，该白血病发病机制的详细分子机制尚不清楚。在其他恶性肿瘤中，肿瘤的发生已被证明是通过多步进展模型进行的，遗传异常的积累与更具侵袭性的临床行为之间存在因果关系。事实证明，恶性细胞中染色体片段的丢失对于定位包含候选抑癌基因的DNA区域是有用的。通过分析高度多态的微卫星标记，可以识别亚微观丢失，从而极大地方便了杂合性丢失(LOH)的检测。利用免疫磁珠分选分离白血病和正常细胞，我们在基于PCR的分析的CLL病例中的8/29(28%)中发现至少一个等位基因丢失。在染色体臂3p上，我们发现了位于新发现的FHIT基因附近的D3S1284基因座的3/29例纯合子缺失。几例CLL均表现为p15和p16抑癌基因端粒缺失，均为早、中期疾病。我们的研究结果表明，在至少一部分病例中，这些基因座的缺失可能与慢性淋巴细胞白血病的发生和/或进展有关。
Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the western world. Details of the molecular mechanisms involved in the pathogenesis of this leukemia are unclear at present. In other malignancies tumorigenesis has been shown to proceed via a multistep progression model with a causal relation between the accumulation of genetic abnormalities and more aggressive clinical behavior. The loss of chromosomal segments in malignant cells has proven useful in mapping regions of DNA that contain candidate tumor suppressor genes. The detection of loss of heterozygosity (LOH) has been greatly facilitated by the analysis of highly polymorphic microsatellite markers enabling the identification of submicroscopic losses. Utilizing immunomagnetic bead sorting to separate leukemic from normal cells we identified at least one allelic losses in 8/29 (28%) of analysed CLL cases with a PCR-based assay. On chromosomal arm 3p we have identified homozygous deletions in 3/29 cases at locus D3S1284 residing in the vicinity of the newly described FHIT gene. Several cases of CLL manifested LOH at a locus telomeric to the p15 and p16 tumor suppressor genes, all being early to intermediate stage disease. Our findings suggest that losses at these loci may contribute to the development and/or progression of CLL in at least a subset of cases.