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.
| Original language | English |
|---|---|
| Pages (from-to) | 1091-1095 |
| Number of pages | 5 |
| Journal | British Journal of Cancer |
| Volume | 89 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Sep 15 2003 |
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Keywords
- Apoptosis
- Ataxia telangiectasia
- Cell cycle
- TCL1
- Telomere
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Telomerase activity, apoptosis and cell cycle progression in ataxia telangiectasia lymphocytes expressing TCL1. / Gabellini, C.; Antonelli, A.; Petrinelli, P.; Biroccio, A.; Marcucci, L.; Nigro, G.; Russo, G.; Zupi, G.; Elli, R.
In: British Journal of Cancer, Vol. 89, No. 6, 15.09.2003, p. 1091-1095.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Telomerase activity, apoptosis and cell cycle progression in ataxia telangiectasia lymphocytes expressing TCL1
AU - Gabellini, C.
AU - Antonelli, A.
AU - Petrinelli, P.
AU - Biroccio, A.
AU - Marcucci, L.
AU - Nigro, G.
AU - Russo, G.
AU - Zupi, G.
AU - Elli, R.
PY - 2003/9/15
Y1 - 2003/9/15
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Ataxia telangiectasia
KW - Cell cycle
KW - TCL1
KW - Telomere
UR - http://www.scopus.com/inward/record.url?scp=0141921837&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0141921837&partnerID=8YFLogxK
U2 - 10.1038/sj.bjc.6601213
DO - 10.1038/sj.bjc.6601213
M3 - Article
C2 - 12966431
AN - SCOPUS:0141921837
VL - 89
SP - 1091
EP - 1095
JO - British Journal of Cancer
JF - British Journal of Cancer
SN - 0007-0920
IS - 6
ER -