MacNamara B, Wang W, Chen Z, Hou M, Mazur J, Gruber A, Porwit-MacDonald A
Department of Pathology, Division of Hematology, Karolinska Hospital and Institutet, Stockholm, Sweden.
Haematologica. 2001 Apr;86(4):386-93.
Telomerase activity (TA) is determined by the catalytic unit telomerase reverse transcriptase (hTERT). In vitro studies show that hTERT is downregulated by wild type p53 and TA is upregulated by BCL-2 expression. The aim of this study was to investigate the relationship of TA and mRNA expression of hTERT, telomerase RNA (hTER) and Tankyrase in 31 samples from patients with high-grade non-Hodgkin's lymphoma (HG-NHL). The results were then related to apoptosis and proliferation and the expression of p53 and BCL-2 family member proteins.
The telomeric repeat amplification protocol (TRAP) assay and reverse transcription-polymerase chain reaction (RT-PCR) were used to quantify TA, and hTERT, hTER and Tankyrase mRNA expression. Proliferation (Ki67), p53, BCL-2, MCL-1, BAX and BAK protein expression were evaluated by immunohistochemistry. Apoptosis was evaluated by TUNEL staining.
TA was detected in 93% of HG-NHL and tended to be higher in p53+ lymphomas. A positive correlation existed between mRNA expression of hTERT, hTER and Tankyrase. hTERT mRNA expression tended to be higher with increasing levels of apoptosis and proliferation, in HG-NHL samples lacking BAX expression and in samples from patients with survival shorter than 3.5 years. hTER mRNA expression was significantly higher in BAX and BAK negative samples.
Telomerase is activated or upregulated in the majority of HG-NHL. Enhanced TA combined with deregulation of the factors responsible for cell survival and proliferation may contribute to the development and progression of lymphomas. Observation that high hTERT mRNA expression may be related to shorter survival should prompt further investigation of the clinical significance of TA and its components in HG-NHL.
端粒酶活性（TA）由催化单位端粒酶逆转录酶（hTERT）决定。体外研究表明，野生型p53可下调hTERT，而BCL-2表达可上调TA。本研究旨在探讨31例高级别非霍奇金淋巴瘤（HG-NHL）患者样本中端粒酶活性与hTERT、端粒酶RNA（hTER）和端锚聚合酶mRNA表达之间的关系。然后将结果与凋亡、增殖以及p53和BCL-2家族成员蛋白的表达相关联。
采用端粒重复序列扩增法（TRAP）和逆转录聚合酶链反应（RT-PCR）定量检测TA以及hTERT、hTER和端锚聚合酶mRNA表达。通过免疫组织化学评估增殖（Ki67）、p53、BCL-2、MCL-1、BAX和BAK蛋白表达。通过TUNEL染色评估凋亡。
93%的HG-NHL中检测到TA，且在p53阳性淋巴瘤中TA往往更高。hTERT、hTER和端锚聚合酶的mRNA表达之间存在正相关。在HG-NHL样本中，随着凋亡和增殖水平的增加、缺乏BAX表达的样本以及生存时间短于3.5年患者的样本中，hTERT mRNA表达往往更高。在BAX和BAK阴性样本中，hTER mRNA表达显著更高。
大多数HG-NHL中端粒酶被激活或上调。增强的TA与负责细胞存活和增殖的因子失调相结合可能有助于淋巴瘤的发生和发展。观察到高hTERT mRNA表达可能与较短生存期相关，这应促使进一步研究TA及其成分在HG-NHL中的临床意义。
