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Telomerase activity and telomere length in lymphocytes from patients with cutaneous T-cell lymphoma
1Department of Dermatology, Marselisborg Hospital, University of Aarhus, Aarhus, Denmark.
Background:
Telomeres shorten with successive cell divisions in normal somatic cells. Telomerase is a ribonucleoprotein enzyme associated with cellular proliferation and plays an important role in maintaining the stability of chromosomes and the length of DNA telomeres. Telomerase activity has been detected in tissues from many human tumors, but is not present in the majority of normal tissues. Thus, measurement of telomerase activity and telomere length may contribute to understanding the mechanism of tumorigenesis and provide useful diagnostic or prognostic information. The aim of this study was to investigate the telomerase activity and telomere length from patients with cutaneous T-cell lymphoma (CTCL).
Methods:
Eighteen skin-homing T-cell lines were established from skin biopsies and 10 peripheral blood mononuclear cells (PBMC) were isolated from patients with various stages of CTCL together with 22 PBMC from healthy donors. For each sample an identical amount of cellular protein was measured quantitatively for telomerase activity using the telomerase polymerase chain reaction-enzyme-linked immunosorbent assay based on the telomeric repeat amplification protocol method. Telomere length was assayed using a commercial kit.
Results:
Eight of ten PBMC and 16 of 18 skin-homing T-cell lines from patients with CTCL showed moderate to strong telomerase activity. Freshly obtained PBMC from healthy donors showed weak levels of telomerase activity. A shorter telomere length was found in cell lines and PBMC from patients with CTCL compared with healthy controls. Four skin-homing T-cell lines going into growth crisis showed sharply reduced telomerase activity.
Conclusions:
The results of the current study indicate that both skin-homing T-cells and PBMC from CTCL have high telomerase activity and short telomere length. These changes are similar to the changes observed in the majority of malignant cells including other types of T-cell lymphoma. It is interesting to note that even in the very early stages of CTCL such as parapsoriasis (which is a clinically benign disease) the changes already are present, indicating that a significantly high level of telomerase activity frequently occurs in CTCL and may be an important event in tumorigenesis. Telomerase activity and telomere length are useful markers for CTCL risk assessment.