Persistent inhibition of telomerase reprograms adult T-cell leukemia to p53-dependent senescence.
作者： Abhik Datta , Marcia Bellon , Uma Sinha-Datta , Ali Bazarbachi , Yves Lepelletier
DOI: 10.1182/BLOOD-2006-01-0067
关键词: Leukemia 、 Cancer research 、 Immunology 、 Senescence 、 Human T-lymphotropic virus 1 、 Cell aging 、 p14arf 、 Biology 、 Telomere 、 T-cell leukemia 、 Telomerase
摘要: The antiviral thymidine analog azidothymidine (AZT) is used to treat several virus-associated human cancers. However, date the mechanism of AZT action remains unclear and thus, reasons for treatment failure are unknown. Adult T-cell leukemia/lymphoma (ATL) an aggressive malignancy poor prognosis. Here, we report that enduring leukemia virus I–infected cells, in vitro vivo ATL patients, results inhibition telomerase activity, progressive telomere shortening, increased p14ARF expression. In turn, this elicits stabilization reactivation tumor suppressor p53-dependent transcription, expression cyclin-dependent kinase inhibitor p21Waf1, accumulation p27kip1, thereby inducing cellular senescence cell death. While patients carrying a wild-type p53 enter remission following with AZT, those mutated did not respond, patients' disease relapse was associated selection clone inactive p53.
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