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Telomerase activity in Hodgkin's disease
K F Norrback1, G Enblad, M Erlanson
1Department of Pathology, Umeâ University, Umeâ, Sweden.
Blood
|July 10, 1998
Summary
Eosinophils degrade telomerase, masking its activity in some Hodgkin's lymphoma cases. Inhibiting ribonucleases reveals telomerase activity, suggesting Hodgkin's lymphoma is a target for anti-telomerase therapies.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Telomere maintenance is crucial for cell immortalization and is primarily mediated by telomerase.
- Telomerase is frequently active in malignant tumors, including most cancer cell lines.
- A telomerase-independent mechanism was previously proposed for Hodgkin's disease due to undetectable telomerase activity in some samples.
Purpose of the Study:
- To investigate the role of telomerase activity in Hodgkin's disease.
- To explore the reasons for undetectable telomerase activity in certain Hodgkin's disease samples.
- To evaluate Hodgkin's lymphoma as a potential target for anti-telomerase therapies.
Main Methods:
- Assessed telomerase activity in 77 Hodgkin's disease samples.
- Investigated the correlation between eosinophilia and telomerase activity.
- Examined the effect of eosinophils and their components (ribonucleases) on telomerase activity.
- Reanalyzed samples using ribonuclease inhibitors.
Main Results:
- Telomerase activity was detected in 31 of 77 Hodgkin's disease samples.
- A strong inverse correlation was found between eosinophilia and detectable telomerase activity.
- Eosinophils and their derived ribonucleases (eosinophil-derived neurotoxin, eosinophilic cationic protein) were shown to degrade telomerase.
- Reanalysis with ribonuclease inhibitors revealed telomerase activity in previously "telomerase-negative" samples from patients with eosinophilia.
- Hodgkin's disease samples without eosinophilia showed decreased telomerase activity compared to non-Hodgkin's lymphomas but increased activity compared to reactive nodes.
- High telomerase expression was observed in Hodgkin's disease cell lines.
Conclusions:
- Ribonuclease-containing cells, particularly eosinophils, significantly impact telomerase detectability in vivo.
- Hodgkin's disease exhibits a telomerase-positive tumor component, even when activity is masked.
- Hodgkin's lymphomas represent potential therapeutic targets for anti-telomerase treatments.