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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 - Br. J. Cancer (2003)

Bottom Line: Individuals affected by ataxia telangiectasia (AT) have a marked susceptibility to cancer.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.

View Article: PubMed Central - PubMed

Affiliation: Experimental Chemotherapy Laboratory, Regina Elena Cancer Institute, Rome, Italy.

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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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.
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fig1: 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.

Mentions: The metaphases with the t(14;14) rearrangement represented 80 and 73% of total AT94-1 lymphocytes, respectively, in 2001 and in 2002. Metaphases with sporadic nonclonal rearrangements were also observed (data not shown). The cytogenetic follow-up of AT94-1 from 1995 to 2000 has been previously reported (Petrinelli et al, 2001).


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 - Br. J. Cancer (2003)

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.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376941&req=5

fig1: 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.
Mentions: The metaphases with the t(14;14) rearrangement represented 80 and 73% of total AT94-1 lymphocytes, respectively, in 2001 and in 2002. Metaphases with sporadic nonclonal rearrangements were also observed (data not shown). The cytogenetic follow-up of AT94-1 from 1995 to 2000 has been previously reported (Petrinelli et al, 2001).

Bottom Line: Individuals affected by ataxia telangiectasia (AT) have a marked susceptibility to cancer.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.

View Article: PubMed Central - PubMed

Affiliation: Experimental Chemotherapy Laboratory, Regina Elena Cancer Institute, Rome, Italy.

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.

Show MeSH
Related in: MedlinePlus