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We show here that TRAIL can trigger apoptosis in a majority of MCL cell lines and primary cultures, irrespective of receptor levels, Bcl-2 family members, or caspase regulator expression. MCL sensitivity to TRAIL was closely linked to the activity of the NF-\u03baB p50 factor and to the consequent expression of cellular FLIP (c-FLIP), which accumulated into the TRAIL-dependent complex in resistant cells. c-FLIP transient knockdown overcame MCL resistance to TRAIL, while NF-\u03baB inhibitors differentially modulated TRAIL cytotoxicity. Indeed, bortezomib increased TRAIL cytotoxic effects in sensitive cells, but led to the intracellular accumulation of c-FLIP, impeding full synergistic interaction. In contrast, the I\u03baB kinase inhibitor BMS-345541 led to decreased c-FLIP expression and allowed all MCL samples to undergo TRAIL-mediated apoptosis. These results present the combination of TRAIL stimulation and I\u03baB kinase inhibition as a new approach to MCL therapy.<\/jats:p>","DOI":"10.4049\/jimmunol.178.3.1923","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:08:45Z","timestamp":1397848125000},"page":"1923-1930","source":"Crossref","is-referenced-by-count":73,"title":["Selective Inhibition of I\u03baB Kinase Sensitizes Mantle Cell Lymphoma B Cells to TRAIL by Decreasing Cellular FLIP Level"],"prefix":"10.1093","volume":"178","author":[{"given":"Gae\u0308l","family":"Roue\u0301","sequence":"first","affiliation":[{"name":"Hematopathology Unit, Hospital Cli\u0301nic, Institut d\u2019Investigacions Biome\u0300diques August Pi i Sunyer, University of Barcelona , Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Pe\u0301rez-Gala\u0301n","sequence":"additional","affiliation":[{"name":"Hematopathology Unit, Hospital Cli\u0301nic, Institut d\u2019Investigacions Biome\u0300diques August Pi i Sunyer, University of Barcelona , Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mo\u0301nica","family":"Lo\u0301pez-Guerra","sequence":"additional","affiliation":[{"name":"Hematopathology Unit, Hospital Cli\u0301nic, Institut d\u2019Investigacions Biome\u0300diques August Pi i Sunyer, University of Barcelona , Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neus","family":"Villamor","sequence":"additional","affiliation":[{"name":"Hematopathology Unit, Hospital Cli\u0301nic, Institut d\u2019Investigacions Biome\u0300diques August Pi i Sunyer, University of Barcelona , Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias","family":"Campo","sequence":"additional","affiliation":[{"name":"Hematopathology Unit, Hospital Cli\u0301nic, Institut d\u2019Investigacions Biome\u0300diques August Pi i Sunyer, University of Barcelona , Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dolors","family":"Colomer","sequence":"additional","affiliation":[{"name":"Hematopathology Unit, Hospital Cli\u0301nic, Institut d\u2019Investigacions Biome\u0300diques August Pi i Sunyer, University of Barcelona , Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2007,2,1]]},"reference":[{"key":"2026012810524688700_R1","first-page":"567","volume-title":"Cancer","year":"1998"},{"key":"2026012810524688700_R2","first-page":"2105","volume-title":"J. 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