Carrasco, Daniel R.Sukhdeo, KumarProtopopova, MarinaEnos, MiriamZheng, MeiMani, MalaIvanova, Elena V.Tonon, GiovanniSinha, RaktimCarrasco, Daniel E.Henderson, JoelPinkus, GeraldineMunshi, NikhilHorner, James W.Protopopov, AlexeiAnderson, KennethDePinho, Ronald A.2012-02-142007Carrasco, Daniel R., Kumar Sukhdeo, Marina Protopopova, Raktim Sinha, Miriam Enos, Daniel E. Carrasco, Mei Zheng, et al. 2007. The Differentiation and Stress Response Factor XBP-1 Drives Multiple Myeloma Pathogenesis. Cancer Cell 11(4): 349-360.1535-6108http://nrs.harvard.edu/urn-3:HUL.InstRepos:8160855Multiple myeloma (MM) evolves from a highly prevalent premalignant condition termed MGUS. The factors underlying the malignant transformation of MGUS are unknown. We report a MGUS/MM phenotype in transgenic mice with Eμ-directed expression of the XBP-1 spliced isoform (XBP-1s), a factor governing unfolded protein/ER stress response and plasma-cell development. Eμ-XBP-1s elicited elevated serum Ig and skin alterations. With age, Eμ-xbp-1s transgenics develop features diagnostic of human MM, including bone lytic lesions and subendothelial Ig deposition. Furthermore, transcriptional profiles of Eμ-xbp-1s lymphoid and MM cells show aberrant expression of known human MM dysregulated genes. The similarities of this model with the human disease, coupled with documented frequent XBP-1s overexpression in human MM, serve to implicate XBP-1s dysregulation in MM pathogenesis.en-UScell cycleJournal Article2012-02-1410.1016/j.ccr.2007.02.015