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Telomerase activity in plasma cell dyscrasias
1Department of Medicine, Division of Hematology, Karolinska Hospital, SE-171 76, Stockholm, Sweden.
British Journal of Cancer
|March 10, 2001
Summary
Telomerase activation is normal in monoclonal gammopathy of undetermined significance (MGUS) but elevated in multiple myeloma (MM) and plasma cell leukaemia (PCL). This suggests telomerase activation is crucial for malignant transformation in these plasma cell disorders.
Area of Science:
- Oncology
- Molecular Biology
- Hematology
Background:
- Telomere maintenance is critical for cellular immortalization and cancer development.
- Plasma cell dyscrasias encompass a spectrum of disorders from premalignant to malignant stages.
Purpose of the Study:
- To investigate telomerase activation in monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM), and plasma cell leukaemia (PCL).
- To understand the role of telomerase in the progression of plasma cell dyscrasias.
Main Methods:
- Assessed telomerase activity in plasma cells from patients with MGUS, MM, and PCL.
- Analyzed the expression of human telomerase reverse transcriptase (hTERT), telomerase RNA template (hTER), and tankyrase in MM/PCL samples.
- Examined telomerase activity in myeloma cell lines.
Main Results:
- Normal telomerase activity was observed in MGUS plasma cells.
- Elevated telomerase activity was detected in 78% of MM patients (21/27) and 100% of PCL patients (4/4).
- High telomerase activity correlated with increased hTERT and hTER expression, and upregulated tankyrase in MM/PCL.
Conclusions:
- MGUS cells likely lack immortalization potential.
- Telomerase activation appears to be a key event in the malignant transformation of MGUS to MM.
- Targeting telomerase may offer therapeutic strategies for multiple myeloma and plasma cell leukaemia.