Telomerase activity and telomere length in lymphocytes from patients with cutaneous T-cell lymphoma

BACKGROUND. Telomeres shorten with successive cell divisions in normal soma tic cells. Telomerase is a ribonucleoprotein enzyme associated with cellula r 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 major ity of normal tissues. Thus, measurement of telomerase activity and telomer e 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 patien ts with cutaneous T-cell lymphoma (CTCL). METHODS. Eighteen skin-homing T-cell lines were established from skin biops ies and 10 peripheral blood mononuclear cells (PBMC) were isolated from pat ients with various stages of CTCL together with 22 PBMC from healthy donors . For each sample an identical amount of cellular protein was measured quan titatively for telomerase activity using the telomerase polymerase chain re action-enzyme-linked immunosorbent assay based on the telomeric repeat ampl ification protocol method. Telomere length was assayed using a commercial k it. RESULTS. Eight of ten PBMC and 16 of 18 skin-homing T-cell lines from patie nts with CTCL showed moderate to strong telomerase activity. Freshly obtain ed PBMC from healthy donors showed weak levels of telomerase activity, A sh orter telomere length was found in cell lines and PBMC from patients with C TCL compared with healthy controls. Four skin-homing T-cell lines going int o growth crisis showed sharply reduced telomerase activity. CONCLUSIONS, The results of the current study indicate that both skin-homin g T-cells and PBMC from CTCL have high telomerase activity and short telome re length. These changes are similar to the changes observed in the majorit y of malignant cells including other types of T-cell lymphoma. It is intere sting to note that even in the very early stages of CTCL such as parapsoria sis (which is a clinically benign disease) the changes already are present, indicating that a significantly high level of telomerase activity frequent ly occurs in CTCL and may be an important event in tumorigenesis. Telomeras e activity and telomere length are useful markers for CTCL risk assessment. (C) 1999 American Cancer Society.