Abstract

Despite the widespread use of proteasome inhibitors in the treatment of multiple myeloma, the mechanisms of the anti-myeloma activity and the molecular pathways that execute the tumor cell killing are still unknown. In the present work we compared gene expression profile changes in response to bortezomib treatment of cultured bone marrow samples from patients with bortezomibsensitive versus bortezomib-resistant myeloma. The results showed a pronounced induction of>70 genes including>30 heat shock protein transcripts in both patient groups and therefore debate the anti-tumor action, attributed to the unfolded protein response. In contrast, a subset of 7 genes (MMP12, IL7R, MGST1, C3, CYP27A1, MIR148A and CXXC4 ) changed only in the samples from

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