Contributions
Abstract: PB2138
Type: Publication Only
Background
The impact of the expression of Lung Resistance Protein (LRP) gene on the development of drug resistance to the first generation proteasome inhibitor Bortezomib is currently under active study.
Aims
To study the impact of LRP gene expression on the sensitivity of tumor plasma cells of bone marrow aspirate of patients with stage III multiple myeloma (MM) and tumor plasma cells of human MM cell lines to Bortezomib.
Methods
The LRP gene expression was assessed in bone marrow mononuclear cell fraction containing plasmocytes of 15 patients with newly diagnosed multiple myeloma Durie-Salmon stage III and in the human MM cell lines RPMI8226 and IM9. The assessment of LRP gene expression was measured by reverse transcription polymerase chain reaction test. The sensitivity of tumor plasmocytes to Bortezomib-action in vivo was assessed by the percentage reduction in the absolute level of paraprotein after 6 courses of Bortezomib-containing treatment, as well as in the overall survival (OS) index. OS were analyzed by the Kaplan-Meier method using the Cox-Mantel criterion. Differences were considered statistically significant at p <0.05. The expression of the LRP gene in MM cell lines was examined before and after prolonged cells culture on a medium with Bortezomib.
Results
The LRP gene expression was found in 10 of 15 patients (67%) before start of cytostatic therapy. The intensity of gene expression was different. Were show 2 subgroups of patients: a subgroup with high LRP gene expression and a subgroup with low intensity of gene expression. After 6 cycles of induction with Bortezomib, there was not a significant decrease of paraprotein levels in the subgroups. Overall survival was negatively associated with high LRP gene expression only (median of overall survival in patients with high LRP gene expression was 17 months and in those with low expression –62 months, р<0.05). In vitro IM9-cells with low LRP expression were more sensitive to Bortezomib- action than RPMI8226-cells with high LRP expression (IC50 were 0.8 ± 0.3x10-8 M and 2.7 ± 0.6x10-8 M respectively). Cultivation of the cell lines on the Bortezomib containing medium for 90 days was leads to increase of IC50 of Bortezomib, as well as to increase of LRP expression in both human MM cell lines.
Conclusion
The high LRP gene expression can impact on the development of tumor plasma cell`s resistance to Bortezomib.
Session topic: 13. Myeloma and other monoclonal gammopathies – Biology & Translational Research
Keyword(s): Cell line, Gene expression, Multiple Myeloma
Abstract: PB2138
Type: Publication Only
Background
The impact of the expression of Lung Resistance Protein (LRP) gene on the development of drug resistance to the first generation proteasome inhibitor Bortezomib is currently under active study.
Aims
To study the impact of LRP gene expression on the sensitivity of tumor plasma cells of bone marrow aspirate of patients with stage III multiple myeloma (MM) and tumor plasma cells of human MM cell lines to Bortezomib.
Methods
The LRP gene expression was assessed in bone marrow mononuclear cell fraction containing plasmocytes of 15 patients with newly diagnosed multiple myeloma Durie-Salmon stage III and in the human MM cell lines RPMI8226 and IM9. The assessment of LRP gene expression was measured by reverse transcription polymerase chain reaction test. The sensitivity of tumor plasmocytes to Bortezomib-action in vivo was assessed by the percentage reduction in the absolute level of paraprotein after 6 courses of Bortezomib-containing treatment, as well as in the overall survival (OS) index. OS were analyzed by the Kaplan-Meier method using the Cox-Mantel criterion. Differences were considered statistically significant at p <0.05. The expression of the LRP gene in MM cell lines was examined before and after prolonged cells culture on a medium with Bortezomib.
Results
The LRP gene expression was found in 10 of 15 patients (67%) before start of cytostatic therapy. The intensity of gene expression was different. Were show 2 subgroups of patients: a subgroup with high LRP gene expression and a subgroup with low intensity of gene expression. After 6 cycles of induction with Bortezomib, there was not a significant decrease of paraprotein levels in the subgroups. Overall survival was negatively associated with high LRP gene expression only (median of overall survival in patients with high LRP gene expression was 17 months and in those with low expression –62 months, р<0.05). In vitro IM9-cells with low LRP expression were more sensitive to Bortezomib- action than RPMI8226-cells with high LRP expression (IC50 were 0.8 ± 0.3x10-8 M and 2.7 ± 0.6x10-8 M respectively). Cultivation of the cell lines on the Bortezomib containing medium for 90 days was leads to increase of IC50 of Bortezomib, as well as to increase of LRP expression in both human MM cell lines.
Conclusion
The high LRP gene expression can impact on the development of tumor plasma cell`s resistance to Bortezomib.
Session topic: 13. Myeloma and other monoclonal gammopathies – Biology & Translational Research
Keyword(s): Cell line, Gene expression, Multiple Myeloma