Multidrug resistance (MDR) is the biological phenomenon, significantly reduces the survival of patients with multiple myeloma (MM) to the conventional chemotherapy. Overexpression of MDR gene (MDR1, MRP1, LRP, BCRP) by plasma cells may be clinically manifest of disease progression during therapy. Proteasome inhibitor Bortezomib for the treatment of MM in clinical practice has greatly improved the survival of patients with this malignant disease, but at the same time, there is a group of patients resistant to the treatment with Bortezomib. The common (total, summary) effect of the expression of 4 MDR genes on the development of drug resistance to the treatment of Bortezomib have not been studied earlier. Aim. Determination of the expression of mRNA genes MDR1, MRP1, LRP, BCRP, responsible for the development of MDR in bone marrow aspirates in patients with newly diagnosed MM before the Bortezomib-containing therapy on the clinical course of the disease and response to the treatment. Materials and methods. Was investigated a group of 15 patients with newly diagnosed stage III MM classification Durie-Salmon before the start of cytostatic therapy. The expression of MDR genes was studied in bone marrow mononuclear cells fraction containing plasma cells, by RT-PCR (polymerase chain reaction reverse transcription). The degree of expression was assessed by semi-quantitative visual assessment from 0 (no electrophoretic strips) to 4 points (bright glow of the transcript). Results. The expression of MDR gene was found in all patients with newly diagnosed MM before the start of cytostatic therapy: MDR 1 gene is expressed in 14 patients (93%), genes MRP 1 and LRP were detected in 11 patients (73%), the expression of BCRP gene was found in 15 patients (100%). The mean value of expression of MRP 1 and BCRP genes according to visual assessment was 1. The mean value of gene expression MDR 1 (M ± SE) is 1.5 ± 0.27 points and LRP gene is 1.47 ± 0.14 points. The common (summary) mean expression of 4 genes was 5.0 ± 0.76 points. According to the expression level - above or below the mean value, we have identified two subgroups of the patients: subgroup A - Patients with higher overall expression of 4 genes and subgroup B - Patients with lower overall MDR genes expression. In these subgroups was analyzed the clinical parameters of disease at the moment of diagnosis, such as the level of hemoglobin, red blood cells, paraprotein, creatinine, calcium, LDH and the effectiveness of the 6 courses of induction therapy with Bortezomib- containing treatment. No significant differences in clinical scores in the subgroups A and B were not found. After induction treatment, in the subgroup A with higher overall MDR genes expression is not detected significant reduction in the absolute value of paraprotein (32,0 ± 3,7 g / l before the treatment, and 19.34 ± 6.47 g /l after the treatment). Whereas, in the subgroup B with lower overall expression, in the same conditions of the treatment, registered a significant reduction of paraprotein value (41,9 ± 5,0 g /l before the treatment, and 14.85 ± 6.53 g / l after the treatment p <0.05). Conclusion. We the first time identified the group of patients with newly diagnosed MM associated with high common expression of MDR genes before to the cytostatic treatment. The common overexpression of 4 MDR genes not associated with such clinical parameters of the disease as the level of hemoglobin, red blood cells, paraprotein, creatinine, calcium, LDH, but it decreases the immediate response to the Bortezomib-containing induction treatment. Disclosures No relevant conflicts of interest to declare.

Background: Increased expression of efflux protein, such as P-glycoprotein, multidrug resistance protein, lung resistance protein, breast cancer resistance protein are a major reason for resistance to existing or previously effective therapy multiple myeloma (MM). Effect of the expression of genes of multidrug resistance (MDR) - MDR1, MRP1, LRP, and BCRP on the efficacy of therapy with proteasome inhibitor is currently not well understood. Aim: Determination of mRNA expression of genes responsible for the development of drug resistance, such as MDR1, MRP1, LRP, BCRP in bone marrow aspirates in patients with newly diagnosed and refractory / relapsed MM before start bortezomib-containing chemotherapy programs. Materials and methods: We studied bone marrow aspirates of 29 patients (12 men and 17 women) aged 48 to 77 years (median 60 years) with stage 3 MM by classification Durie-Salmon. 14 of studied patients made a group of newly diagnosed MM. 15 patients made a clinically refractory / relapsed group MM. The bone marrow in this group of patients was studied after treatment with alkylating agents at the time of registration of resistance to the given therapy. In the future, all patients were treated by bortezomib - containing chemtheapy regimens. mRNA expression studied genes was determined by semi-quantitative polymerase chain reaction reverse transcription. Results: In both groups of patients had comparable expression of all studied MDR`s genes. In the group of newly diagnose patients the MDR 1 mRNA expression was detected in 93% (13/14) of the samples, the mRNA of the gene MRP 1 was detected in 79% (11/14). The BCRP mRNA expression was detected in 100% of the investigated samples. The expression of mRNA of the gene LRP was identified in 71% of the studied cases (10/14). In the group of patients after treatment with alkylating agents the expression of mRNA of MDR1 was detected in 87% (13/15) of samples, MRP 1 was detected in 93% (14/15), BCRP was in 100% of cases, and the LRP mRNA was detected in 13/15 (87%) of the samples.Treatment efficacy was assessed by Iinternational Unified Response Criteria for multiple myeloma after the 6 cycles of treatment. Evaluation of treatment efficacy in patients previously non-treated with chemotherapy as well as in the group of clinical resistance patients showed comparable results by the number of objective response rate (57% and 60% respectively). Conclusions: The expression of MDR genes does not determine the resistance of tumor cells to bortezomib. The proteasome inhibitor bortezomib can overcome the MDR gene activity, attaching it to alkylating drugs increases the sensitivity to them of resistant tumor cells. Disclosures Golenkov: Novartis: Consultancy.