CpG island methylation of the hTERT promoter is associated with lower telomerase activity in B-cell lymphocytic leukemia
CpG island methylation of the hTERT promoter is associated with lower telomerase activity in B-cell lymphocytic leukemia
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DOI：
10.1016/s0301-472x(01)00760-3
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发表时间：
2002-01-01
影响因子：
2.6
通讯作者：
Thaler, J
中科院分区：
文献类型：
--
作者：
Bechter, OE;Eisterer, W;Thaler, J
Objective.端粒酶催化亚基hTERT的表达对于延长复制寿命是必不可少的，并且是细胞永生化和癌发生的限速步骤。因为hTERT表达与端粒酶活性正相关，所以其调节被认为是酶活性的主要决定因素。hTERT启动子区含有两个CpG岛，已知它们是从头DNA甲基化的靶位点。为了阐明这种表观遗传机制对端粒酶活性的影响，我们分析了30例慢性B细胞淋巴细胞白血病患者hTERT启动子甲基化的程度。使用甲基化特异性竞争性聚合酶链反应测定评估hTERT启动子甲基化。该检测方法是基于在用内标扩增之前用甲基化敏感的限制性内切酶消化基因组DNA。表现出高端粒酶活性的患者比低酶活性的患者表现出显著更少的hTERT启动子核心结构域甲基化。此外，端粒酶活性与端粒长度和总体生存率显着相关。结论。我们的数据表明，hTERT启动子的CpG岛甲基化程度表现出对端粒酶活性的影响，在一个亚组的B细胞慢性淋巴细胞白血病患者，因此被认为是发挥作用，在这些患者的hTERT基因表达的调节。(C)2002年国际实验血液学学会。出版社：Elsevier Science Inc.
Objective. Expression of the catalytic subunit of the telomerase enzyme hTERT is essential for prolonging the replicative lifespan and is the rate-limiting step in cellular immortalization and carcinogenesis. Because hTERT expression is positively correlated with telomerase activity, its regulation is suggested as the major determinant of enzymatic activity. The hTERT promoter region contains two CpG islands, which are known to be target sites for de novo DNA methylation. To elucidate the impact of this epigenetic mechanism on telomerase activity, we analyzed the degree of hTERT promoter methylation in 30 patients with B-cell chronic lymphocytic leukemia.Materials and Methods. hTERT promoter methylation was assessed using a methylation-specific competitive polymerase chain reaction assay. The assay is based on digestion of genomic DNA with a methylation-sensitive restriction enzyme before amplification with an internal standard.Results. Patients exhibiting, high telomerase activity showed significantly less methylation of the hTERT promoter core domain than patients with low enzyme activity. In addition, telomerase activity was significantly associated with telomere length and overall survival.Conclusions. Our data show that the degree of CpG island methylation of the hTERT promoter exhibits an impact on telomerase activity in a subgroup of patients with B-cell chronic lymphocytic leukemia and therefore is assumed to play a role in regulating hTERT gene expression in these patients. (C) 2002 International Society for Experimental Hematology. Published by Elsevier Science Inc.