Contributions
Abstract: PB1943
Type: Publication Only
Background
Aims
We evaluated the changes of intensity of expression of MDR genes in patients with newly diagnosed and refractory/relapsed multiple myeloma and the effect of expression of MDR genes such as MDR 1, MRP 1, BCRP, LRP on the overall survival of patients after treatment with bortezomib.
Methods
The bone marrow aspirates of 30 patients (12 men and 18 women) aged 48 to 77 years (median 60 years) with stage III MM by classification Durie-Salmon were studied. 15 patients were included in a group of newly diagnosed (ND) MM. 15 patients were in group of a clinically refractory/ relapsed (RR) MM. The bone marrow in this group of patients were 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 chemotherapy regimens. mRNA expression studied genes were determined by semi-quantitative 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). The overall survival (OS) was analyzed by the Kaplan-Meier method, with the use of Cox-Mantel test. Differences were considered statistically significant at p <0.05.
Results
In both groups of patients had comparable expression of all studied MDR`s genes. The development of clinical resistance to treatment with alkylating agents were accompanied by an increase in mRNA expression of all studied genes. However, the statistically significant increase the expression of the intensity obtained for LRP gene only (the average intensity of the expression of mRNA LRP gene in ND MM 0.9 ± 0.24, with RR MM 1.93 ± 0.34, p <0.05). The MDR 1 mRNA expression was 1.50 ± 0.34 in the group of ND MM and 1.67 ± 0.31 in the group of RR MM, p> 0.05. The expression of mRNA of MRP 1 and BCRP are 1.07 ± 0.21 and 1.63 ± 0.15 respectively before treatment and increased to 1.73 ± 0.31 and 2.13 ± 0.35 respectively in the group of RR MM, p = 0,06. OS was negatively associated with high LRP gene expression only in group of ND MM (median of OS in patients with high LRP gene expression was 17 months and in those with low expression 62 months, p <0.05).
Conclusion
High expression of LRP gene is associated with worse overall survival in patients with newly diagnosed MM treated with bortezomib- containing chemotherapy programs. 'Genetic resource MDR' in MM is due mainly to the initial multidrug resistance. The treatment of MM by alkylating drugs increase the existing at the time of diagnosis of MDR activity of genes.
Session topic: 13. Myeloma and other monoclonal gammopathies - Biology
Keyword(s): Multiple Myeloma, Multidrug resistance, bortezomib
Abstract: PB1943
Type: Publication Only
Background
Aims
We evaluated the changes of intensity of expression of MDR genes in patients with newly diagnosed and refractory/relapsed multiple myeloma and the effect of expression of MDR genes such as MDR 1, MRP 1, BCRP, LRP on the overall survival of patients after treatment with bortezomib.
Methods
The bone marrow aspirates of 30 patients (12 men and 18 women) aged 48 to 77 years (median 60 years) with stage III MM by classification Durie-Salmon were studied. 15 patients were included in a group of newly diagnosed (ND) MM. 15 patients were in group of a clinically refractory/ relapsed (RR) MM. The bone marrow in this group of patients were 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 chemotherapy regimens. mRNA expression studied genes were determined by semi-quantitative 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). The overall survival (OS) was analyzed by the Kaplan-Meier method, with the use of Cox-Mantel test. Differences were considered statistically significant at p <0.05.
Results
In both groups of patients had comparable expression of all studied MDR`s genes. The development of clinical resistance to treatment with alkylating agents were accompanied by an increase in mRNA expression of all studied genes. However, the statistically significant increase the expression of the intensity obtained for LRP gene only (the average intensity of the expression of mRNA LRP gene in ND MM 0.9 ± 0.24, with RR MM 1.93 ± 0.34, p <0.05). The MDR 1 mRNA expression was 1.50 ± 0.34 in the group of ND MM and 1.67 ± 0.31 in the group of RR MM, p> 0.05. The expression of mRNA of MRP 1 and BCRP are 1.07 ± 0.21 and 1.63 ± 0.15 respectively before treatment and increased to 1.73 ± 0.31 and 2.13 ± 0.35 respectively in the group of RR MM, p = 0,06. OS was negatively associated with high LRP gene expression only in group of ND MM (median of OS in patients with high LRP gene expression was 17 months and in those with low expression 62 months, p <0.05).
Conclusion
High expression of LRP gene is associated with worse overall survival in patients with newly diagnosed MM treated with bortezomib- containing chemotherapy programs. 'Genetic resource MDR' in MM is due mainly to the initial multidrug resistance. The treatment of MM by alkylating drugs increase the existing at the time of diagnosis of MDR activity of genes.
Session topic: 13. Myeloma and other monoclonal gammopathies - Biology
Keyword(s): Multiple Myeloma, Multidrug resistance, bortezomib