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Comparative Study
. 2003 Sep 15;89(6):1091-5.
doi: 10.1038/sj.bjc.6601213.

Telomerase activity, apoptosis and cell cycle progression in ataxia telangiectasia lymphocytes expressing TCL1

C Gabellini  1 , A Antonelli, P Petrinelli, A Biroccio, L Marcucci, G Nigro, G Russo, G Zupi, R Elli
Affiliations
Comparative Study

Telomerase activity, apoptosis and cell cycle progression in ataxia telangiectasia lymphocytes expressing TCL1

C Gabellini et al. Br J Cancer. .

Abstract

Individuals affected by ataxia telangiectasia (AT) have a marked susceptibility to cancer. Ataxia telangiectasia cells, in addition to defects in cell cycle checkpoints, show dysfunction of apoptosis and of telomeres, which are both thought to have a role in the progression of malignancy. In 1-5% of patients with AT, clonal expansion of T lymphocytes carrying t(14;14) chromosomal translocation, deregulating TCL1 gene(s), has been described. While it is known that these cells can progress with time to a frank leukaemia, the molecular pathway leading to tumorigenesis has not yet been fully investigated. In this study, we compared AT clonal cells, representing 88% of the entire T lymphocytes (AT94-1) and expressing TCL1 oncogene (ATM(-) TCL1(+)), cell cycle progression to T lymphocytes of AT patients without TCL1 expression (ATM(-) TCL1(-)) by analysing their spontaneous apoptosis rate, spontaneous telomerase activity and telomere instability. We show that in ATM(-) TCL1(+) lymphocytes, apoptosis rate and cell cycle progression are restored back to a rate comparable with that observed in normal lymphocytes while telomere dysfunction is maintained.

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Figures

Figure 1
Figure 1
TRAP assay to evaluate the effect of ATM status and TCL1 expression on telomerase activity in human PHA-stimulated lymphocytes. From left to right: a negative control; a sample of normal lymphocytes; two samples of AT lymphocytes (AT95-1, AT95-2); a sample of AT lymphocytes expressing TCL1 (AT94-1); a positive control.
Figure 2
Figure 2
Evaluation of apoptosis and DNA content of different types of lymphocytes. (A) Results of a representative TUNEL assay performed on four samples of normal lymphocytes, two of AT lymphocytes (AT95-1 and AT95-2) and one of TCL1 expressing AT lymphocytes (AT94-1). (B) TUNEL-positive cell percentage (dark grey columns), cell percentage in the G0/G1 phase (white columns) and in the S–G2/M phase (grey columns) of cell cycle. Each experiment was performed at least three times.
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