Bechter O E, Eisterer W, Pall G, Hilbe W, Kühr T, Thaler J
Department of General Internal Medicine, Innsbruck University Hospital, Austria.
Cancer Res. 1998 Nov 1;58(21):4918-22.
The telomere-telomerase hypothesis states that the vast majority of human tumors have a prolonged replicative life span throughout expressing telomerase, which compensates the cell division-associated loss of telomere DNA. The use of telomere length and telomerase expression as new biological markers in cancer patients requires their correlation with disease prognosis. We, therefore, correlated the mean telomere length based on a telomere restriction fragment assay and the activity of telomerase measured with a telomeric repeat amplification protocol with clinical data and overall survival in 58 patients with B cell chronic lymphocytic leukemia (B-CLL). Telomere length showed a highly inverse correlation to telomerase activity. Patients with telomeres below 6.0 kb were associated with high telomerase activity, whereas patients with a telomere length >6.0 kb generally showed low enzyme activity (P <0.001). Patients in Binet A exhibited significantly longer telomeres and had less telomerase activity than did patients in Binet B or Binet C, where significantly shorter telomeres and higher telomerase activity were observed (P=0.031). Short telomere length and high telomerase activity were significantly associated with a shorter median survival (P=0.02 and P <0.001), and telomerase activity was the most significant prognostic factor for overall survival in B-CLL (P <0.001). Our data provide evidence that telomere length, as well telomerase activity, exerts a strong impact on the survival of B-CLL patients and that telomerase activity can be used as a new prognostic marker in this disease.
端粒-端粒酶假说指出，绝大多数人类肿瘤在整个表达端粒酶的过程中具有延长的复制寿命，端粒酶可补偿与细胞分裂相关的端粒DNA损失。将端粒长度和端粒酶表达用作癌症患者的新生物标志物需要它们与疾病预后相关联。因此，我们基于端粒限制片段分析的平均端粒长度以及用端粒重复序列扩增法测量的端粒酶活性与58例B细胞慢性淋巴细胞白血病（B-CLL）患者的临床数据和总生存期进行了关联分析。端粒长度与端粒酶活性呈高度负相关。端粒长度低于6.0 kb的患者与高端粒酶活性相关，而端粒长度>6.0 kb的患者通常显示低酶活性（P<0.001）。与Binet B或Binet C期患者相比，Binet A期患者的端粒明显更长，端粒酶活性更低，在Binet B或Binet C期观察到端粒明显更短且端粒酶活性更高（P=0.031）。短端粒长度和高端粒酶活性与较短的中位生存期显著相关（P=0.02和P<0.001），并且端粒酶活性是B-CLL患者总生存期最重要的预后因素（P<0.001）。我们的数据提供了证据，表明端粒长度以及端粒酶活性对B-CLL患者的生存有强烈影响，并且端粒酶活性可作为该疾病的一种新的预后标志物。
