PROGNOSTIC SIGNIFICANCE OF EXPRESSION OF MULTIDRUG RESISTANCE GENES IN PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA TREATED WITH BORTEZOMIB-CONTEINING THERAPHY
(Abstract release date: 05/19/16)
EHA Library. Chernykh Y. 06/09/16; 134880; PB1980
Yulia Chernykh
Contributions
Contributions
Abstract
Abstract: PB1980
Type: Publication Only
Background
Most drugs used to treat multiple myeloma, are substrates for protein multi-drug resistance. Their effectiveness is reduced in cells with increased expression of genes encoding these proteins. The proteasome inhibitor bortezomib is not a substrate for protein P-gp, encoded by MDR 1 gene.
Aims
The aim of our study was to examine the prognostic significance of the alternative (non-P-gp dependent) mechanisms of multidrug resistance (MDR) in the bone marrow aspirate in patients with newly diagnosed multiple myeloma (MM).
Methods
The study included 15 patients (6 men and 9 women) with established diagnosis of multiple myeloma stage III by Durie‐Salmon system. The age of patients ranged from 50 to 78 years. The mRNA expression of MDR genes, 1 MRP, BCRP, LRP was determined by semi-quantitative RT-PCR in mononuclear fraction of the bone marrow aspirate. Numeric value corresponding to the amount of mRNA expression of each studied gene, represented as the ratio of the numerical values of the mRNA expression of each gene to a numeric value of mRNA expression of the gene GAPDH. All patients subsequently received treatment with bortezomib-containing chemotherapy schemes in the amount of 6 courses.
Results
Although the patients had not received cytostatic therapy, detected mRNA expression of all studied genes MDR. The average number of MDR gene transcripts was 1.7±0,24, MRP 1 1±0,14, BCPR 1,04±0,22, LRP 1,47±0,17 points. Because previous studies have shown that the proteasome inhibitor bortezomib is a basic drug for the treatment of MM is not a substrate of P-gp, the analysis of survival in subgroups of patients with the number of LRP gene transcripts above and below the mean. Overall survival of patients with increased expression of the gene was significantly worse than that of whom with reduced expression of LRP (17,1±3,65 vs 53, 9±10 months, P˂0.005 ).
Conclusion
Increased expression of LRP gene exert a poor survival of patients with multiple myeloma for cytostatic treatment, the bortezomib - containing chemotherapy programs.
Session topic: E-poster
Keyword(s): Bortezomib, Multidrug resistance, Multiple myeloma
Type: Publication Only
Background
Most drugs used to treat multiple myeloma, are substrates for protein multi-drug resistance. Their effectiveness is reduced in cells with increased expression of genes encoding these proteins. The proteasome inhibitor bortezomib is not a substrate for protein P-gp, encoded by MDR 1 gene.
Aims
The aim of our study was to examine the prognostic significance of the alternative (non-P-gp dependent) mechanisms of multidrug resistance (MDR) in the bone marrow aspirate in patients with newly diagnosed multiple myeloma (MM).
Methods
The study included 15 patients (6 men and 9 women) with established diagnosis of multiple myeloma stage III by Durie‐Salmon system. The age of patients ranged from 50 to 78 years. The mRNA expression of MDR genes, 1 MRP, BCRP, LRP was determined by semi-quantitative RT-PCR in mononuclear fraction of the bone marrow aspirate. Numeric value corresponding to the amount of mRNA expression of each studied gene, represented as the ratio of the numerical values of the mRNA expression of each gene to a numeric value of mRNA expression of the gene GAPDH. All patients subsequently received treatment with bortezomib-containing chemotherapy schemes in the amount of 6 courses.
Results
Although the patients had not received cytostatic therapy, detected mRNA expression of all studied genes MDR. The average number of MDR gene transcripts was 1.7±0,24, MRP 1 1±0,14, BCPR 1,04±0,22, LRP 1,47±0,17 points. Because previous studies have shown that the proteasome inhibitor bortezomib is a basic drug for the treatment of MM is not a substrate of P-gp, the analysis of survival in subgroups of patients with the number of LRP gene transcripts above and below the mean. Overall survival of patients with increased expression of the gene was significantly worse than that of whom with reduced expression of LRP (17,1±3,65 vs 53, 9±10 months, P˂0.005 ).
Conclusion
Increased expression of LRP gene exert a poor survival of patients with multiple myeloma for cytostatic treatment, the bortezomib - containing chemotherapy programs.
Session topic: E-poster
Keyword(s): Bortezomib, Multidrug resistance, Multiple myeloma
Abstract: PB1980
Type: Publication Only
Background
Most drugs used to treat multiple myeloma, are substrates for protein multi-drug resistance. Their effectiveness is reduced in cells with increased expression of genes encoding these proteins. The proteasome inhibitor bortezomib is not a substrate for protein P-gp, encoded by MDR 1 gene.
Aims
The aim of our study was to examine the prognostic significance of the alternative (non-P-gp dependent) mechanisms of multidrug resistance (MDR) in the bone marrow aspirate in patients with newly diagnosed multiple myeloma (MM).
Methods
The study included 15 patients (6 men and 9 women) with established diagnosis of multiple myeloma stage III by Durie‐Salmon system. The age of patients ranged from 50 to 78 years. The mRNA expression of MDR genes, 1 MRP, BCRP, LRP was determined by semi-quantitative RT-PCR in mononuclear fraction of the bone marrow aspirate. Numeric value corresponding to the amount of mRNA expression of each studied gene, represented as the ratio of the numerical values of the mRNA expression of each gene to a numeric value of mRNA expression of the gene GAPDH. All patients subsequently received treatment with bortezomib-containing chemotherapy schemes in the amount of 6 courses.
Results
Although the patients had not received cytostatic therapy, detected mRNA expression of all studied genes MDR. The average number of MDR gene transcripts was 1.7±0,24, MRP 1 1±0,14, BCPR 1,04±0,22, LRP 1,47±0,17 points. Because previous studies have shown that the proteasome inhibitor bortezomib is a basic drug for the treatment of MM is not a substrate of P-gp, the analysis of survival in subgroups of patients with the number of LRP gene transcripts above and below the mean. Overall survival of patients with increased expression of the gene was significantly worse than that of whom with reduced expression of LRP (17,1±3,65 vs 53, 9±10 months, P˂0.005 ).
Conclusion
Increased expression of LRP gene exert a poor survival of patients with multiple myeloma for cytostatic treatment, the bortezomib - containing chemotherapy programs.
Session topic: E-poster
Keyword(s): Bortezomib, Multidrug resistance, Multiple myeloma
Type: Publication Only
Background
Most drugs used to treat multiple myeloma, are substrates for protein multi-drug resistance. Their effectiveness is reduced in cells with increased expression of genes encoding these proteins. The proteasome inhibitor bortezomib is not a substrate for protein P-gp, encoded by MDR 1 gene.
Aims
The aim of our study was to examine the prognostic significance of the alternative (non-P-gp dependent) mechanisms of multidrug resistance (MDR) in the bone marrow aspirate in patients with newly diagnosed multiple myeloma (MM).
Methods
The study included 15 patients (6 men and 9 women) with established diagnosis of multiple myeloma stage III by Durie‐Salmon system. The age of patients ranged from 50 to 78 years. The mRNA expression of MDR genes, 1 MRP, BCRP, LRP was determined by semi-quantitative RT-PCR in mononuclear fraction of the bone marrow aspirate. Numeric value corresponding to the amount of mRNA expression of each studied gene, represented as the ratio of the numerical values of the mRNA expression of each gene to a numeric value of mRNA expression of the gene GAPDH. All patients subsequently received treatment with bortezomib-containing chemotherapy schemes in the amount of 6 courses.
Results
Although the patients had not received cytostatic therapy, detected mRNA expression of all studied genes MDR. The average number of MDR gene transcripts was 1.7±0,24, MRP 1 1±0,14, BCPR 1,04±0,22, LRP 1,47±0,17 points. Because previous studies have shown that the proteasome inhibitor bortezomib is a basic drug for the treatment of MM is not a substrate of P-gp, the analysis of survival in subgroups of patients with the number of LRP gene transcripts above and below the mean. Overall survival of patients with increased expression of the gene was significantly worse than that of whom with reduced expression of LRP (17,1±3,65 vs 53, 9±10 months, P˂0.005 ).
Conclusion
Increased expression of LRP gene exert a poor survival of patients with multiple myeloma for cytostatic treatment, the bortezomib - containing chemotherapy programs.
Session topic: E-poster
Keyword(s): Bortezomib, Multidrug resistance, Multiple myeloma
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