@article{oai:nagasaki-u.repo.nii.ac.jp:00016466,
 author = {Hasegawa, Hiroo and Yamada, Yasuaki and Iha, Hidekatsu and Tsukasaki, Kunihiro and Nagai, Kazuhiro and Atogami, Sunao and Sugahara, Kazuyuki and Tsuruda, Kazuto and Ishizaki, Akiko and Kamihira, Shimeru},
 issue = {11},
 journal = {Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K},
 month = {Nov},
 note = {It has been reported that the induction of cellular senescence through p53 activation is an effective strategy in tumor regression. Unfortunately, however, tumors including adult T-cell leukemia/lymphoma (ATL) have disadvantages such as p53 mutations and a lack of p16(INK4a) and/or p14(ARF). In this study we characterized Nutlin-3a-induced cell death in 16 leukemia/lymphoma cell lines. Eight cell lines, including six ATL-related cell lines, had wild-type p53 and Nutlin-3a-activated p53, and the cell lines underwent apoptosis or cell-cycle arrest, whereas eight cell lines with mutated p53 were resistant. Interestingly, senescence-associated-beta-galactosidase (SA-beta-gal) staining revealed that only ATL-related cell lines with wild-type p53 showed cellular senescence, although they lack both p16(INK4a) and p14(ARF). These results indicate that cellular senescence is an important event in p53-dependent cell death in ATL cells and is inducible without p16(INK4a) and p14(ARF). Furthermore, knockdown of Tp53-induced glycolysis and apoptosis regulator (TIGAR), a novel target gene of p53, by small interfering RNA(siRNA) indicated its important role in the induction of cellular senescence. As many patients with ATL carry wild-type p53, our study suggests that p53 activation by Nutlin-3a is a promising strategy in ATL. We also found synergism with a combination of Nutlin-3a and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), suggesting the application of Nutlin-3a-based therapy to be broader than expected.Leukemia advance online publication, 27 August 2009; doi:10.1038/leu.2009.171., Leukemia, 23(11), pp.2090?2101; 2009},
 pages = {2090--2101},
 title = {Activation of p53 by Nutlin-3a, an antagonist of MDM2, induces apoptosis and cellular senescence in adult T-cell leukemia cells.},
 volume = {23},
 year = {2009}
}