The investigation of bortezomib activation mechanisim in 13q deletion positive multiple myeloma patients

Multiple myeloma (MM) is a malignant hematological disorder characterized by the clonal proliferation of malignant plasma cells. Despite conventional and high dose therapies MM remains incurable disease with a median survival of 3-7 years and resistance of tumor cells to various treatments. Developing drug resistance in MM represents the main obstacle to satisfactory treatment. In order to clarify the pathogenesis of acquired drug resistance in MM, further detailed studies should be performed.Study findings have shown that abnormalities of chromosome 13 are associated with reduced life span, poor prognosis and lower responses to conventional therapies. Also recent studies suggest that ICAM and NF-kB molecules are important factors in the pathogenesis of acquired drug resistance in MM.The aim of this study is to evaluate the interaction between bortezomib, which is the promising novel agent for multiple myeloma treatment, and 13q deletion, the expression of ICAM and the activation of NF-kB.In this study, bone marrow samples from 18 patients with MM were used. Mononuclear cells were isolated by Ficoll separation and cultured overnight. Before and after treating bortezomib, ICAM levels are evaluated by immunohistochemistry and the activation of NF-kB was investigated by ELISA. In addition, 13q deletion was detected by FISH.According to our results, 44% of MM patients were positive for 13q deletion. The relation ship between the presence of 13q deletion and the activation of NF-kB was not significant. But, before treatment, the expression levels of ICAM were higher than after treating bortezomib in patients with 13q deletion negative. On the other hand, in patients with 13q deletion positive, the level of calcium, CRP and plasma cells in bone marrow were significantly higher.Our study findings suggest, there can be association between the presence of 13q deletion and acquired drug resistance. Furthermore, NF-kB activation and the expression of ICAM should be investigated in large patient series studies.Keywords: Multipl myeloma, 13q deletion, ICAM, NF-kB, Drug resistance