Role of Nuclear Heme Oxygenase 1 (HO-1) in Bortezomib Induced Cell Death and Genomic Instability of Multiple Myeloma (MM) Cells

Abstract

In patients with MM we measured selected parameters of MBD in comparison with the stage of the disease according to Durie-Salmon (DS) and according to International Staging System (ISS). In MGUS we assessed the relationship of the parameters to the risk of transformation to MM based on the Mayo clinic stratification system. Weassessed following parameters ofMBD:hepatocyte growth factor (HGF, Human HGF Quantine ELISA), macrophage inflammatory factor alpha (MIP-1 , Human CCL3/MIP-1 Quantikine ELISA), syndecan-1 (Human Syndecan-1 (CD138) ELISA), osteoprotegerin (OPG,HumanOsteoprotegerin ELISA), Activin A (Human Activin A Quantikine ELISA), Dickkopf-related protein-1 (DKK1, Human Dkk-1 Quantikine ELISA), Annexin A2 (Human Annexin A2 ELISA kit), nuclear factor kappa B (NFB, Human Nuclear factor-kappa B). For statistical estimation we used Kruskal-Wallis test and MannWhitney U post hoc test with Bonferroni correction at p < 0,05. Results: Within the comparison of MM and MGUS we found significant differences in serum levels of HGF (median 1⁄4 M 2997 vs 1757pg/mL), MIP-1 (M 25,5 vs 21,1pg/mL), syndecan-1 (M 77,3 vs 24,2ng/mL), and NFB (M 0,61 vs 0,26ng/mL). There was a trend towards increasing serum levels of these parameters when comparing MGUS, SMM and AMM, the difference between MGUS and SMM and the difference between SMM and AMM were not, however, statistically significant. With regard to the activity of the disease there was a significant relationship of syndecan-1 to DS, and significant relationship of HGF, MIP-1, syndecan-1, OPG and Activin A to ISS. Neither of the parameters had significant relationship to Mayo clinic risk stratification in MGUS individuals. Conclusions: The selected parameters of MBD showed relationship to the activity of MM with certain discriminatory potential of MM and MGUS. The most perspective parameters were HGF, MIP-1, syndecan-1, OPG, Activin A and NFB. There were no differences in these parameters in MGUS with regard to the risk of transformation into MM. Supported by the grant NT 14393.