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We have shown that this disease is responsive to the combination of zidovudine and interferon\u2010\u03b1. However, long\u2010term maintenance therapy with this combination is associated with side effects affecting patient quality of life and hence more tolerated alternatives are needed. In this submission, we explored the effect of the mammalian target of rapamycin (mTOR) complex\u20101 (mTORC1) inhibitor everolimus (RAD001) on ATL and HTLV\u2010negative malignant T\u2010cell lines. We demonstrate that, at clinically achievable concentrations, long\u2010term treatment with everolimus resulted in a dramatic inhibitory effect on the growth of HTLV\u2010I\u2010positive and \u2010negative malignant T\u2010cells, while normal resting or activated T\u2010lymphocytes were resistant. Everolimus specifically induced oncoprotein Tax degradation and senescence in ATL cells and cell cycle arrest and apoptosis in HTLV\u2010I\u2010negative malignant T\u2010cells. Everolimus\u2010mediated apoptosis was also associated with an upregulation of p53 upregulated modulator of apoptosis (PUMA\u2010\u03b1) proteins, an increase in Bax proteins and downregulation of Bcl\u2010x<jats:sub>L<\/jats:sub>proteins in all tested HTLV\u2010I\u2010positive and \u2010negative malignant cell lines. These results support a therapeutic role for everolimus, particularly as long\u2010term maintenance therapy in patients with ATL and other HTLV\u2010I\u2010negative peripheral T\u2010cell lymphomas.<\/jats:p>","DOI":"10.1002\/ijc.25742","type":"journal-article","created":{"date-parts":[[2010,11,9]],"date-time":"2010-11-09T16:13:07Z","timestamp":1289319187000},"page":"1006-1017","source":"Crossref","is-referenced-by-count":23,"title":["Inhibition of mammalian target of rapamycin signaling by everolimus induces senescence in adult T\u2010cell leukemia\/lymphoma and apoptosis in peripheral T\u2010cell 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