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.
Highlights
Multidrug resistance (MDR) is a natural phenomenon in development of solid and hematologic tumors
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
Patients were treated with bortezomib-containing chemotherapy hereafter
Summary
Множественная лекарственная устойчивость (МЛУ) является закономерным событием в развитии солидных и гематологических опухолей, существенно влияющим на непосредственные и отдаленные результаты лечения. Цель – определение экспрессии матричной рибонуклеиновой кислоты (мРНК) генов MDR1, MRP1, LRP, BCRP, ответственных за развитие МЛУ в аспирате костного мозга резистентных пациентов до начала бортезомибсодержащей терапии. Изучение экспрессии генов МЛУ проводили в клетках мононуклеарной фракции костного мозга, содержащей плазмоциты, методом полимеразной цепной реакции с обратной транскрипцией. Экспрессия мРНК генов MDR1, MRP1, BCRP была выявлена у всех пациентов, а гена LRP – у 81%. Было выделено две группы пациентов: с уровнем экспрессии генов МЛУ выше и ниже среднего. Обнаружена 100% экспрессия генов MDR1, MRP1, BCRP у резистентных пациентов с ММ. Медиана выживаемости в группах пациентов с уровнем экспрессии мРНК генов МЛУ выше и ниже среднего существенно и достоверно различается. Ключевые слова: множественная миелома, костный мозг, множественная лекарственная устойчивость, бортезомибсодержащая терапия
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