Telomerase activity in relation to pro- and anti-apoptotic protein expression in high grade non-Hodgkin's lymphomas

Abstract

BACKGROUND AND OBJECTIVES: 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. DESIGN AND METHODS: 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. RESULTS: 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. INTERPRETATION AND CONCLUSIONS: 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.