Bcl-2high mantle cell lymphoma cells are sensitized to acadesine with ABT-199

摘要: // Arnau Montraveta 1 , Silvia Xargay-Torrent Laia Rosich Monica Lopez-Guerra 1,2 Jocabed Roldan Vanina Rodriguez Eriong Lee-Verges Merce de Frias 3 Clara Campas Elias Campo 2 Gael Roue and Dolors Colomer Experimental Therapeutics in Lymphoid Malignancies Group, Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain Unitat d’Hematopatologia, Hospital Clinic, IDIBAPS, Advancell-Advanced In Vitro Cell Technologies S.A., Correspondence to: Colomer, email: Keywords : acadesine (AICAR), mantle cell lymphoma, Mcl-1, ABT-199, Bcl-2 Received March 23, 2015 Accepted May 13, Published 22, Abstract Acadesine is a nucleoside analogue with known activity against B-cell malignancies. Herein, we showed that lymphoma (MCL) cells induced caspase-dependent apoptosis through turning on the mitochondrial apoptotic machinery. At molecular level, compound triggered activation of AMPK pathway, consequently modulating downstream targets, such as mTOR motility-related vasodilator-stimulated phosphoprotein (VASP). VASP phosphorylation by was concomitant blockade CXCL12-induced migration. The inhibition cascade acadesine, committed MCL to enter translational downregulation antiapoptotic Mcl-1 protein. contrast, protein levels were unaffected samples expressing high tended have reduced response drug. Targeting selective BH3-mimetic agent ABT-199 sensitized acadesine. This effect validated vivo where combination both agents displayed more marked tumor outgrowth than each drug alone. These findings support notions proteins family regulate sensitivity this inhibitors might be an interesting therapeutic option treat patients.