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Here we show that GX15-070 induced apoptosis in vitro in MCL cell lines and primary cells from patients with MCL by releasing Bak from Mcl-1 and Bcl-XL at short incubation times and low micromolar doses. GX15-070 was effective in cells bearing defective DNA damage-sensor genes or cell-cycle regulators, inducing Bax and Bak conformational changes, mitochondrial depolarization, phosphatidylserine exposure, and caspase-3 activation. Furthermore, GX15-070 synergized with bortezomib, sensitizing MCL cells to low doses of this proteasome inhibitor, by neutralizing bortezomib-induced Mcl-1 accumulation and cooperating with Noxa to induce Bak displacement from this protein. These events led to an increased activation of the mitochondrial apoptotic pathway. Importantly, GX15-070 alone or in combination with bortezomib showed no significant cytotoxic effect in peripheral blood mononuclear cells from healthy donors. All these findings suggest that GX15-070 alone or in combination with bortezomib represents a new attractive therapeutic approach for MCL treatment.<\/jats:p>","DOI":"10.1182\/blood-2006-07-034173","type":"journal-article","created":{"date-parts":[[2007,1,17]],"date-time":"2007-01-17T03:09:23Z","timestamp":1169003363000},"page":"4441-4449","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":162,"title":["The BH3-mimetic GX15-070 synergizes with bortezomib in mantle cell lymphoma by enhancing Noxa-mediated activation of Bak"],"prefix":"10.1182","volume":"109","author":[{"given":"Patricia","family":"Pe\u0301rez-Gala\u0301n","sequence":"first","affiliation":[{"name":"Hematopathology Unit, Department of Pathology, Hospital Cli\u0301nic, Institut d'Investigacions Biome\u0300diques August Pi i Sunyer (IDIBAPS), University of Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gae\u0308l","family":"Roue\u0301","sequence":"additional","affiliation":[{"name":"Hematopathology Unit, Department of Pathology, Hospital Cli\u0301nic, Institut d'Investigacions Biome\u0300diques August Pi i Sunyer (IDIBAPS), University of Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neus","family":"Villamor","sequence":"additional","affiliation":[{"name":"Hematopathology Unit, Department of Pathology, Hospital Cli\u0301nic, Institut d'Investigacions Biome\u0300diques August Pi i Sunyer (IDIBAPS), University of Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias","family":"Campo","sequence":"additional","affiliation":[{"name":"Hematopathology Unit, Department of Pathology, Hospital Cli\u0301nic, Institut d'Investigacions Biome\u0300diques August Pi i Sunyer (IDIBAPS), University of Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dolors","family":"Colomer","sequence":"additional","affiliation":[{"name":"Hematopathology Unit, Department of Pathology, Hospital Cli\u0301nic, Institut d'Investigacions Biome\u0300diques August Pi i Sunyer (IDIBAPS), University of Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","published-online":{"date-parts":[[2007,1,16]]},"reference":[{"key":"2019111711573874800_B1","unstructured":"Campo E, Raffeld M, Jaffe ES. 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