title: Telomerase activity, apoptosis and cell cycle progression in ataxia telangiectasia lymphocytes expressing TCL1.
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.
authors.affiliation: Experimental Chemotherapy Laboratory, Regina Elena Cancer Institute, Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Gabellini
authors.forename: A
authors.initials: A
authors.lastname: Antonelli
authors.forename: P
authors.initials: P
authors.lastname: Petrinelli
authors.forename: A
authors.initials: A
authors.lastname: Biroccio
authors.forename: L
authors.initials: L
authors.lastname: Marcucci
authors.forename: G
authors.initials: G
authors.lastname: Nigro
authors.forename: G
authors.initials: G
authors.lastname: Russo
authors.forename: G
authors.initials: G
authors.lastname: Zupi
authors.forename: R
authors.initials: R
authors.lastname: Elli
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis; D001260:Ataxia Telangiectasia / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002883:Chromosomes, Human, Pair 14; D002999:Clone Cells; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005047:Etoposide / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D011289:Preleukemia / Q000235:genetics; D011518:Proto-Oncogene Proteins; D013601:T-Lymphocytes / Q000201:enzymology* / Q000378:metabolism; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014178:Translocation, Genetic
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C090851:TCL1A protein, human; D014157:Transcription Factors; D005047:Etoposide; D019098:Telomerase