THE EFFECT OF MULTIDRUG RESISTANCE GENE EXPRESSION ON THE CLINICAL COURSE OF MULTIPLE MYELOMA

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Abstract

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.

About the authors

Yu. B. Chernykh

Moscow Regional Research and Clinical Institute (MONIKI); 61/2 Shchepkina ul., Moscow, 129110, Russian Federation

Author for correspondence.
Email: yulia_chernih@mail.ru
MD, Research Fellow, Department of Clinical Hematology and Immunotherapy Россия

A. K. Golenkov

Moscow Regional Research and Clinical Institute (MONIKI); 61/2 Shchepkina ul., Moscow, 129110, Russian Federation

Email: yulia_chernih@mail.ru
MD, PhD, Professor, Head of Department of Clinical Hematology and Immunotherapy Россия

S. S. Shushanov

N.N. Blokhin Russian Cancer Research Center; 24 Kashirskoe shosse, Moscow, 115478, Russian Federation

Email: yulia_chernih@mail.ru
PhD, Doctor of Biol. Sci., Leading Research Fellow, Laboratory of Tumor Cells Genetics Россия

T. A. Kravtsova

N.N. Blokhin Russian Cancer Research Center; 24 Kashirskoe shosse, Moscow, 115478, Russian Federation

Email: yulia_chernih@mail.ru
Junior Research Fellow, Laboratory of Tumor Cells Genetics Россия

E. Yu. Rybalkina

N.N. Blokhin Russian Cancer Research Center; 24 Kashirskoe shosse, Moscow, 115478, Russian Federation

Email: yulia_chernih@mail.ru
PhD (in Biol.), Senior Research Fellow, Laboratory of Tumor Cells Genetics Россия

A. F. Karamysheva

N.N. Blokhin Russian Cancer Research Center; 24 Kashirskoe shosse, Moscow, 115478, Russian Federation

Email: yulia_chernih@mail.ru
PhD, Doctor of Biol. Sci., Head of Laboratory of Tumor Cells Genetics Россия

T. A. Mitina

Moscow Regional Research and Clinical Institute (MONIKI); 61/2 Shchepkina ul., Moscow, 129110, Russian Federation

Email: yulia_chernih@mail.ru
MD, PhD, Senior Research Fellow, Department of Clinical Hematology and Immunotherapy Россия

E. V. Trifonova

Moscow Regional Research and Clinical Institute (MONIKI); 61/2 Shchepkina ul., Moscow, 129110, Russian Federation

Email: yulia_chernih@mail.ru
MD, PhD, Senior Research Fellow, Department of Clinical Hematology and Immunotherapy Россия

E. V. Kataeva

Moscow Regional Research and Clinical Institute (MONIKI); 61/2 Shchepkina ul., Moscow, 129110, Russian Federation

Email: yulia_chernih@mail.ru
MD, PhD, Senior Research Fellow, Department of Clinical Hematology and Immunotherapy Россия

L. L. Vysotskaya

Moscow Regional Research and Clinical Institute (MONIKI); 61/2 Shchepkina ul., Moscow, 129110, Russian Federation

Email: yulia_chernih@mail.ru
MD, PhD, Research Fellow, Department of Clinical Hematology and Immunotherapy Россия

A. A. Stavrovskaya

N.N. Blokhin Russian Cancer Research Center; 24 Kashirskoe shosse, Moscow, 115478, Russian Federation

Email: yulia_chernih@mail.ru
MD, PhD, Professor, Leading Research Fellow, Laboratory of Tumor Cells Genetics Россия

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Copyright (c) 2016 Chernykh Y.B., Golenkov A.K., Shushanov S.S., Kravtsova T.A., Rybalkina E.Y., Karamysheva A.F., Mitina T.A., Trifonova E.V., Kataeva E.V., Vysotskaya L.L., Stavrovskaya A.A.

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