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We evaluated the killing effect of this proteasome inhibitor on EBV\u2010associated T lymphoma cells and NK lymphoma cells. First, we found that bortezomib treatment decreased the viability of multiple T and NK cell lines. No significant difference was observed between EBV\u2010positive and EBV\u2010negative cell lines. The decreased viability in response to bortezomib treatment was abrogated by a pan\u2010caspase inhibitor. The induction of apoptosis was confirmed by flow cytometric assessment of annexin V staining. Additionally, cleavage of caspases and polyadenosine diphosphate\u2010ribose polymerase, increased expression of phosphorylated I\u03baB, and decreased expression of inhibitor of apoptotic proteins were detected by immunoblotting in bortezomib\u2010treated cell lines. We found that bortezomib induced lytic infection in EBV\u2010positive T cell lines, although the existence of EBV did not modulate the killing effect of bortezomib. Finally, we administered bortezomib to peripheral blood mononuclear cells from five patients with EBV\u2010associated lymphoproliferative diseases. Bortezomib had a greater killing effect on EBV\u2010infected cells. These results indicate that bortezomib killed T or NK lymphoma cells by inducing apoptosis, regardless of the presence or absence of EBV.<\/jats:p>","DOI":"10.1002\/ijc.25873","type":"journal-article","created":{"date-parts":[[2010,12,17]],"date-time":"2010-12-17T16:20:07Z","timestamp":1292602807000},"page":"2263-2273","source":"Crossref","is-referenced-by-count":32,"title":["Bortezomib induces apoptosis in T lymphoma cells and natural killer lymphoma cells independent of Epstein\u2010Barr virus 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