A Subset of Genes Can Distinguish between Bortezomib Responsive Versus Bortezomib Resistant Myeloma
Yossi Cohen *
Institute of Hematology, Assaf Harofeh Medical Center, Affiliated to Sackler Faculty of Medicine, Tel Aviv University, Israel.
Odit Gutwein
Institute of Hematology, Assaf Harofeh Medical Center, Affiliated to Sackler Faculty of Medicine, Tel Aviv University, Israel.
Osnat Garach- Jehoshua
Hematology Laboratory, Assaf Harofeh Medical Center, Affiliated to Sackler Faculty of Medicine, Tel Aviv University, Israel.
Adina Bar-Haim
Department of Chemistry, Assaf Harofeh Medical Center, Affiliated to Sackler Faculty of Medicine, Tel Aviv University, Israel.
Abraham Kornberg
Institute of Hematology, Assaf Harofeh Medical Center, Affiliated to Sackler Faculty of Medicine, Tel Aviv University, Israel.
*Author to whom correspondence should be addressed.
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 bortezomib-sensitive 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 the bortezomib-sensitive cases and therefore these tumor-associated genes might serve as predictors of the treatment efficacy, as well as for making of further insights onto the mechanism of action of proteasome inhibitors. In summary, we identified a subset of 7 genes which distinguished in our small series betweensensitive versus resistant tumor cells to bortezomib, which requires further assessment in a larger cohort of patients.
Keywords: Multiple myeloma, gene expression profile, MMP12, heat shock proteins, IL7R