Email this article EXPRESSION OF GENES RESPONSIBLE FOR MULTIDRUG RESISTANCE IN RELAPSED/REFRACTORY MULTIPLE MYELOMA PATIENTS
- Authors: Chernykh Y.B.1, Shushanov S.S.2
-
Affiliations:
- Moscow Regional Research and Clinical Institute (MONIKI)
- N.N. Blokhin Russian Cancer Research Center of RAMS
- Issue: No 31 (2014)
- Pages: 47-51
- Section: ARTICLES
- URL: https://almclinmed.ru/jour/article/view/61
- DOI: https://doi.org/10.18786/2072-0505-2014-31-47-51
- ID: 61
Cite item
Full Text
Abstract
Background: Multidrug resistance (MDR) is a natural phenomenon in development of solid and hematologic tumors. This phenomenon significantly influences both immediate and remote outcome of treatment. In this connection, an interest arises to studying this problem in multiple myeloma (MM) patients with expressed clinical signs of tumorous progression, the main of them being an absence or loss of the response to antitumor treatment. Aim: To study the expression of messenger RNA (mRNA) of a series of MDR genes, namely MDR1, MRP1, LRP, BCRP responsible for MDR development in the bone marrow aspirate of resistant patients prior to bortezomib-containing chemotherapy. Materials and methods: Study group included 19 relapsed/refractory multiple myeloma patients. Investigation of MDR genes expression was carried out on the cells of the bone marrow mononuclear fraction containing plasmocytes. The mRNA level was analyzed by semiquantitative RT-PCR (polymerase chain reaction with reverse transcription). Patients were treated with bortezomib-containing chemotherapy hereafter. Results: mRNA expression of genes MDR1, MRP1, BCRP was revealed in all (100%) patients, and that of gene LRP – in 81% of myeloma samples. The levels of MDR genes mRNA expression were different. On this basis, two groups of patients were identified: with the levels of MDR genes expression above and beyond the average. Conclusion: 100%-expression of MDR genes (MDR1, MRP1, BCRP) mRNA was revealed in drug resistant MM patients. The median survival in group of patients with higher levels of MDR genes mRNA expression versus lower levels of MDR genes mRNA expression was statistically significant.
About the authors
Yu. B. Chernykh
Moscow Regional Research and Clinical Institute (MONIKI)
Author for correspondence.
Email: yulia_chernih@mail.ru
scientific worker, Department of Clinical Hematology and Immunotherapy of MONIKI Russian Federation
S. S. Shushanov
N.N. Blokhin Russian Cancer Research Center of RAMS
Email: fake@neicon.ru
PhD, senior scientific worker, Laboratory of tumor cell genetics, Blokhin RCRC Russian Federation
References
- Митина Т.А., Голенков А.К., Трифонова Е.В., Луцкая Т.Д., Катаева Е.В., Высоцкая Л.Л., Дудина Г.А., Черных Ю.Б., Захаров С.Г., Клинушкина Е.Ф., Белоусов К.А. Эффективность бортезомиба, мелфалана и преднизолона (ВМП) у пациентов с впервые выявленной множественной миеломой. Биомедицинский журнал Medline.ru 2013;14:1030-50. [Mitina T.A., Golenkov A.K., Trifonova E.V., Lutskaya T.D., Kataeva E.V., Vysotskaya L.L., Dudina G.A., Chernykh Yu.B., Zakharov S.G., Klinushkina E.F., Belousov K.A. Efficiency of Bortezomib, Melphalan and Prednisolon (BMP) in patients with primarily revealed multiple myeloma. Biomeditsinskiy zhurnal Medline.ru 2013;14:1030-50 (in Russian)].
- Голенков А.К., Митина Т.А., Когарко И.Н., Любимова Н.В., Клинушкина Е.Ф., Барышников А.Ю. Фармакодинамическая характеристика эффективности велкейда при резистентной и рецидивной множественной миеломе: определение свободных легких цепей иммуноглобулинов сыворотки крови. Терапевтический архив 2009;81(7):37-41. [Golenkov A.K., Mitina T.A., Kogarko I.N., Lyubimova N.V., Klinushkina E.F., Baryshnikov A.Yu. Pharmacodynamic characteristic of Velcade efficiency in resistant and recurrent multiple myeloma: detection of free light chains of serum immunoglobulins. Terapevticheskiy arkhiv 2009;81(7):37-41 (in Russian)].
- Панищева Л.А., Какпакова Е.С., Рыбалкина Е.Ю., Ставровская A.А. Влияние ингибитора протеасом бортезомиба на экспрессию и активность АВС-транспортеров в опухолевых клетках. Биологические мембраны 2010;27(2):195-201. [Panishcheva L.A., Kakpakova E.S., Rybalkina E.Yu., Stavrovskaya A.A. Effect of inhibitors of bortezomib proteasomes on the expression and activity of ABC-transporters in tumor cells. Biologicheskie membrany 2010;27(2):195-201 (in Russian)].
- Ставровская А.А. Множественная лекарственная устойчивость, обусловленная активностью транспортных белков клетки: некоторые новые факты и перспективы исследований. Биологические мембраны 2003;20(3)196-205. [Stavrovskaya A.A. Multidrug resistance due to the activity of cellular transport proteins: some new facts and study perspectives. Biologicheskie membrany 2003;20(3):196-205 (in Russian)].
- Schwarzenbach H. Expression of MDR1/P-glycoprotein, the multi-drug resistance protein MRP, and the lung-resistance protein LRP in multiple myeloma. Med Oncol 2002;19(2):87-104.
- Sonneveld P. Multidrug resistance in haematological malignancies. J Intern Med 2000;247(5):521-34.
- Ставровская А.А. Опухолевая клетка в обороне. Соросовский образовательный журнал 2001;(7):17-23. [Stavrovskaya A.A. Tumor cell in the defense. Sorosovskiy obrazovatelnyy zhurnal 2001;(7):17-23 (in Russian)].
- Hatok J., Račay P., Hudeček J., Dobrota D. Genes of multidrug resistance in haematological malignancies. Biologia (Bratislava) 2006;61(3):247-56.
- Durie B.G., Salmon S.E. A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer 1975;36(3):842-54.
- Шушанов C.C., Марьина Л.Г., Черных Ю.Б., Какпакова Е.С. Коэкспрессия МРНК генов систем IGF/инсулин и множественной лекарственной устойчивости у больных множественной миеломой. Клиническая онкогематология 2010; 3(2):105-113. [Shushanov C.C., Mar'ina L.G., Cher nykh Yu.B., Kakpakova E.S. Co-expression of mRNA genes of the systems both IGF/insulin and multidrug resistance in patients with multiple myeloma. Klinicheskaya onkogematologiya 2010;3(2):105-113 (in Russian)].
Supplementary files
