THE EFFECT OF MULTIDRUG RESISTANCE GENE EXPRESSION ON THE CLINICAL COURSE OF MULTIPLE MYELOMA
Background: Implementation of a proteasome inhibitor bortezomib into treatment of multiple myeloma has helped to improve survival of patients with this malignancy that is characterized by continuous relapsing course as a clinical manifestation of multidrug resistance (MDR). Previous studies have res...
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| Format: | Article |
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MONIKI
2017-01-01
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| Series: | Alʹmanah Kliničeskoj Mediciny |
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| Online Access: | https://www.almclinmed.ru/jour/article/view/452 |
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| author | Yu. B. Chernykh A. K. Golenkov S. S. Shushanov T. A. Kravtsova E. Yu. Rybalkina A. F. Karamysheva T. A. Mitina E. V. Trifonova E. V. Kataeva L. L. Vysotskaya A. A. Stavrovskaya |
| author_facet | Yu. B. Chernykh A. K. Golenkov S. S. Shushanov T. A. Kravtsova E. Yu. Rybalkina A. F. Karamysheva T. A. Mitina E. V. Trifonova E. V. Kataeva L. L. Vysotskaya A. A. Stavrovskaya |
| author_sort | Yu. B. Chernykh |
| collection | DOAJ |
| description | Background: Implementation of a proteasome inhibitor bortezomib into treatment of multiple myeloma has helped to improve survival of patients with this malignancy that is characterized by continuous relapsing course as a clinical manifestation of multidrug resistance (MDR). Previous studies have resulted in contradictory data on the effects of various MDR genes expression on efficacy of bortezomib. Aim: To evaluate an impact of MDR1, MRP1, LRP, BCRP gene mRNA expression responsible for the development of MDR in bone marrow aspirates from patients with newly diagnosed multiple myeloma before bortezomib-containing therapy on the clinical course of the disease, response to treatment and overall survival. Materials and methods: MDR gene expression was assessed in a group of 15 patients with newly diagnosed multiple myeloma Durie-Salmon stage III before initiation of a bortezomib-based chemotherapeutic regimen. The assessment was done in bone marrow mononuclear cell fraction containing plasmocytes. MDR gene expression was measured by reverse transcription polymerase chain reaction test. Results: MDR gene expression was found in all patients with newly diagnosed multiple myeloma before initiation of cytostatic therapy: MDR1 was expressed in 14 (93%) of patients, MRP1 and LRP – in 11 (73%), BCRP – in 15 (100%). There was no difference between patient subgroups with high and low MDR gene expression in their clinical parameters, such as hemoglobin level, erythrocyte counts, total calcium, creatinine, total protein, lactate dehydrogenase, and albumin. At diagnosis of multiple myeloma, only absolute levels of paraprotein were significantly lower in patients with high MDR1 gene expression (31.52±3 vs 44.27±3.62 g/L, p<0.05). After 6 cycles of induction, there was a significant decrease of paraprotein levels in the group with low MDR1 gene expression (from 44.3±3.6 to 16.8±5.2 g/L, p<0.05). 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). Conclusion: High expression of MDR genes in patients with newly diagnosed multiple myeloma is not associated with clinical characteristics of the disease but may deteriorate the immediate response to bortezomib-based regimens and overall survival. |
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| spelling | doaj.art-94caa4122f9e4aa3848952bfd3104a3a2022-12-21T20:14:17ZrusMONIKIAlʹmanah Kliničeskoj Mediciny2072-05052587-92942017-01-0144562463010.18786/2072-0505-2016-44-5-624-630411THE EFFECT OF MULTIDRUG RESISTANCE GENE EXPRESSION ON THE CLINICAL COURSE OF MULTIPLE MYELOMAYu. B. Chernykh0A. K. Golenkov1S. S. Shushanov2T. A. Kravtsova3E. Yu. Rybalkina4A. F. Karamysheva5T. A. Mitina6E. V. Trifonova7E. V. Kataeva8L. L. Vysotskaya9A. A. Stavrovskaya10Moscow Regional Research and Clinical Institute (MONIKI); 61/2 Shchepkina ul., Moscow, 129110, Russian FederationMoscow Regional Research and Clinical Institute (MONIKI); 61/2 Shchepkina ul., Moscow, 129110, Russian FederationN.N. Blokhin Russian Cancer Research Center; 24 Kashirskoe shosse, Moscow, 115478, Russian FederationN.N. Blokhin Russian Cancer Research Center; 24 Kashirskoe shosse, Moscow, 115478, Russian FederationN.N. Blokhin Russian Cancer Research Center; 24 Kashirskoe shosse, Moscow, 115478, Russian FederationN.N. Blokhin Russian Cancer Research Center; 24 Kashirskoe shosse, Moscow, 115478, Russian FederationMoscow Regional Research and Clinical Institute (MONIKI); 61/2 Shchepkina ul., Moscow, 129110, Russian FederationMoscow Regional Research and Clinical Institute (MONIKI); 61/2 Shchepkina ul., Moscow, 129110, Russian FederationMoscow Regional Research and Clinical Institute (MONIKI); 61/2 Shchepkina ul., Moscow, 129110, Russian FederationMoscow Regional Research and Clinical Institute (MONIKI); 61/2 Shchepkina ul., Moscow, 129110, Russian FederationN.N. Blokhin Russian Cancer Research Center; 24 Kashirskoe shosse, Moscow, 115478, Russian FederationBackground: Implementation of a proteasome inhibitor bortezomib into treatment of multiple myeloma has helped to improve survival of patients with this malignancy that is characterized by continuous relapsing course as a clinical manifestation of multidrug resistance (MDR). Previous studies have resulted in contradictory data on the effects of various MDR genes expression on efficacy of bortezomib. Aim: To evaluate an impact of MDR1, MRP1, LRP, BCRP gene mRNA expression responsible for the development of MDR in bone marrow aspirates from patients with newly diagnosed multiple myeloma before bortezomib-containing therapy on the clinical course of the disease, response to treatment and overall survival. Materials and methods: MDR gene expression was assessed in a group of 15 patients with newly diagnosed multiple myeloma Durie-Salmon stage III before initiation of a bortezomib-based chemotherapeutic regimen. The assessment was done in bone marrow mononuclear cell fraction containing plasmocytes. MDR gene expression was measured by reverse transcription polymerase chain reaction test. Results: MDR gene expression was found in all patients with newly diagnosed multiple myeloma before initiation of cytostatic therapy: MDR1 was expressed in 14 (93%) of patients, MRP1 and LRP – in 11 (73%), BCRP – in 15 (100%). There was no difference between patient subgroups with high and low MDR gene expression in their clinical parameters, such as hemoglobin level, erythrocyte counts, total calcium, creatinine, total protein, lactate dehydrogenase, and albumin. At diagnosis of multiple myeloma, only absolute levels of paraprotein were significantly lower in patients with high MDR1 gene expression (31.52±3 vs 44.27±3.62 g/L, p<0.05). After 6 cycles of induction, there was a significant decrease of paraprotein levels in the group with low MDR1 gene expression (from 44.3±3.6 to 16.8±5.2 g/L, p<0.05). 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). Conclusion: High expression of MDR genes in patients with newly diagnosed multiple myeloma is not associated with clinical characteristics of the disease but may deteriorate the immediate response to bortezomib-based regimens and overall survival.https://www.almclinmed.ru/jour/article/view/452multiple myelomamultidrug resistancebortezomib-based regimen |
| spellingShingle | Yu. B. Chernykh A. K. Golenkov S. S. Shushanov T. A. Kravtsova E. Yu. Rybalkina A. F. Karamysheva T. A. Mitina E. V. Trifonova E. V. Kataeva L. L. Vysotskaya A. A. Stavrovskaya THE EFFECT OF MULTIDRUG RESISTANCE GENE EXPRESSION ON THE CLINICAL COURSE OF MULTIPLE MYELOMA Alʹmanah Kliničeskoj Mediciny multiple myeloma multidrug resistance bortezomib-based regimen |
| title | THE EFFECT OF MULTIDRUG RESISTANCE GENE EXPRESSION ON THE CLINICAL COURSE OF MULTIPLE MYELOMA |
| title_full | THE EFFECT OF MULTIDRUG RESISTANCE GENE EXPRESSION ON THE CLINICAL COURSE OF MULTIPLE MYELOMA |
| title_fullStr | THE EFFECT OF MULTIDRUG RESISTANCE GENE EXPRESSION ON THE CLINICAL COURSE OF MULTIPLE MYELOMA |
| title_full_unstemmed | THE EFFECT OF MULTIDRUG RESISTANCE GENE EXPRESSION ON THE CLINICAL COURSE OF MULTIPLE MYELOMA |
| title_short | THE EFFECT OF MULTIDRUG RESISTANCE GENE EXPRESSION ON THE CLINICAL COURSE OF MULTIPLE MYELOMA |
| title_sort | effect of multidrug resistance gene expression on the clinical course of multiple myeloma |
| topic | multiple myeloma multidrug resistance bortezomib-based regimen |
| url | https://www.almclinmed.ru/jour/article/view/452 |
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