Telomerase activity, apoptosis and cell cycle progression in ataxia telangiectasia lymphocytes expressing TCL1.
Telomerase activity, apoptosis and cell cycle progression in ataxia telangiectasia lymphocytes expressing TCL1.
复制标题
表达TCL1的链球菌淋巴细胞的端粒酶活性，凋亡和细胞周期进程。
DOI：
10.1038/sj.bjc.6601213
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发表时间：
2003-09-15
影响因子：
8.8
通讯作者：
Elli, R
中科院分区：
文献类型：
--
作者：
Gabellini, C;Antonelli, A;Petrinelli, P;Biroccio, A;Marcucci, L;Nigro, G;Russo, G;Zupi, G;Elli, R
患有共济失调性毛细血管扩张症 (AT) 的个体对癌症具有明显的易感性。共济失调毛细血管扩张细胞除了细胞周期检查点缺陷外，还表现出细胞凋亡和端粒功能障碍，这两者被认为在恶性肿瘤的进展中发挥作用。据报道，在 1-5% 的 AT 患者中，携带 t(14;14) 染色体易位的 T 淋巴细胞发生克隆扩增，导致 TCL1 基因失调。虽然已知这些细胞可以随着时间的推移进展为明显的白血病，但导致肿瘤发生的分子途径尚未得到充分研究。在本研究中，我们通过分析其自发凋亡率、自发端粒酶活性和端粒不稳定性，比较了占整个T淋巴细胞（AT94-1）88％并表达TCL1癌基因（ATM−TCL1+）的AT克隆细胞与不表达TCL1的AT患者T淋巴细胞（ATM−TCL1−）的细胞周期进展。我们发现，在 ATM−TCL1+ 淋巴细胞中，凋亡率和细胞周期进展恢复到与正常淋巴细胞中观察到的水平相当，同时端粒功能障碍得以维持。
Individuals affected by ataxia telangiectasia (AT) have a marked susceptibility to cancer. Ataxia telangiectasia cells, in addition to defects in cell cycle checkpoints, show dysfunction of apoptosis and of telomeres, which are both thought to have a role in the progression of malignancy. In 1–5% of patients with AT, clonal expansion of T lymphocytes carrying t(14;14) chromosomal translocation, deregulating TCL1 gene(s), has been described. While it is known that these cells can progress with time to a frank leukaemia, the molecular pathway leading to tumorigenesis has not yet been fully investigated. In this study, we compared AT clonal cells, representing 88% of the entire T lymphocytes (AT94-1) and expressing TCL1 oncogene (ATM− TCL1+), cell cycle progression to T lymphocytes of AT patients without TCL1 expression (ATM− TCL1−) by analysing their spontaneous apoptosis rate, spontaneous telomerase activity and telomere instability. We show that in ATM− TCL1+ lymphocytes, apoptosis rate and cell cycle progression are restored back to a rate comparable with that observed in normal lymphocytes while telomere dysfunction is maintained.