{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:45:33Z","timestamp":1787013933988,"version":"build-2736575974"},"reference-count":48,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,8,25]],"date-time":"2014-08-25T00:00:00Z","timestamp":1408924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    Epstein\u2010Barr virus (EBV) latent proteins exert anti\u2010apoptotic effects on EBV\u2010transformed lymphoid cells by down\u2010regulating BCL2L11 (BIM), CDKN2A (p16\n                    <jats:sup>INK4A<\/jats:sup>\n                    ) and CDKN1A (p21\n                    <jats:sup>WAF1<\/jats:sup>\n                    ). However, the potential therapeutic effects of targeting these anti\u2010apoptotic mechanisms remain unexplored. Here, we tested both\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    effects of the combination of histone deacetylase (HDAC) and proteasome inhibitors on the apoptosis of six endemic Burkitt lymphoma (BL) lines of different latency patterns (types I and III and Wp\u2010restricted) and three lymphoblastoid cell lines (LCLs). We found that the combination of HDAC and proteasome inhibitors (e.g. SAHA\/bortezomib) synergistically induced the killing of Wp\u2010restricted and latency III BL and LCLs but not latency I BL cells. The synergistic killing was due to apoptosis, as evidenced by the high percentage of annexin V positivity and strong cleavage of PARP1 (PARP) and CASP3 (caspase\u20103). Concomitantly, SAHA\/bortezomib up\u2010regulated the expression of CDKN2A and CDKN1A but did not affect the level of BCL2L11 or BHRF1 (viral homologue of BCL2). The apoptotic effects were dependent on reactive oxygen species generation. Furthermore, SAHA\/bortezomib suppressed the growth of Wp\u2010restricted BL xenografts in nude mice. This study provides the rationale to test the novel application of SAHA\/bortezomib on the treatment of EBV\u2010associated Wp\u2010restricted BL and post\u2010transplant lymphoproliferative disorder.\n                  <\/jats:p>","DOI":"10.1111\/bjh.13089","type":"journal-article","created":{"date-parts":[[2014,8,25]],"date-time":"2014-08-25T02:03:22Z","timestamp":1408932202000},"page":"639-650","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Combination of\n                    <scp>SAHA<\/scp>\n                    and bortezomib up\u2010regulates\n                    <scp>CDKN2A<\/scp>\n                    and\n                    <scp>CDKN1A<\/scp>\n                    and induces apoptosis of Epstein\u2010Barr virus\u2010positive Wp\u2010restricted Burkitt lymphoma and lymphoblastoid cell lines"],"prefix":"10.1111","volume":"167","author":[{"given":"Kwai Fung","family":"Hui","sequence":"first","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine Li Ka Shing Faculty of Medicine The University of Hong Kong Queen Mary Hospital Pokfulam Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne Y.","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine Li Ka Shing Faculty of Medicine The University of Hong Kong Queen Mary Hospital Pokfulam Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po L.","family":"Yeung","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine Li Ka Shing Faculty of Medicine The University of Hong Kong Queen Mary Hospital Pokfulam Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaap M.","family":"Middeldorp","sequence":"additional","affiliation":[{"name":"Department of Pathology VU University Medical Centre Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan K.S.","family":"Chiang","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine Li Ka Shing Faculty of Medicine The University of Hong Kong Queen Mary Hospital Pokfulam Hong Kong SAR 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