bloodjourГематология и трансфузиологияRussian journal of hematology and transfusiology0234-57302411-3042ООО Издательский дом «Практика»10.35754/0234-5730-2019-64-1-79-89bloodjour-128Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESМОЛЕКУЛЯРНЫЕ МАРКЕРЫ БОРТЕЗОМИБ-ИНДУЦИРОВАННОЙ ПОЛИНЕЙРОПАТИИ У БОЛЬНЫХ МНОЖЕСТВЕННОЙ МИЕЛОМОЙMOLECULAR FEATURES OF BORTEZOMIB-INDUCED NEUROPATHY IN PATIENTS WITH MULTIPLE MYELOMAhttps://orcid.org/0000-0002-9890-4264НазароваЕ. Л.NazarovaE. L.

Назарова Елена Львовна, кандидат медицинских наук, заведующая лабораторией клеточной и молекулярной иммунологии

Elena L. Nazarova, Cand. Sci. (Med.), Head of the Laboratory of Cellular and Molecular Immunology

nazarova@niigpk.ruhttps://orcid.org/0000-0002-8479-3217МинаеваН. В.MinaevaN. V.

Минаева Наталья Викторовна, кандидат медицинских наук, заместитель директора по лечебной работе

Natalia V. Minaeva, Cand. Sci. (Med.), Deputy Director for Clinical Work

minaeva@niigpk.ruhttps://orcid.org/0000-0001-9692-2541ЗотинаЕ. Н.ZotinaE. N.

Зотина Екатерина Николаевна, кандидат медицинских наук, руководитель научно-клинического отдела

Ekaterina N. Zotina, Cand. Sci. (Med.), Head of the Scientific and Clinical Department

zotina@niigpk.ruhttps://orcid.org/0000-0002-1447-0199ДокшинаИ. А.DokshinaI. A.

Докшина Ирина Анатольевна, кандидат медицинских наук, старший научный сотрудник научно-клинического отдела

Irina A. Dokshina, Cand. Sci. (Med.), Senior Researcher, Scientific and Clinical Department

dokshina@niigpk.ruhttps://orcid.org/0000-0002-8479-3217СухоруковаЭ. Е.SuhorukovaE. E.

Сухорукова Эмилия Евгеньевна, кандидат медицинских наук, научный сотрудник лаборатории клеточной и молекулярной иммунологии

Emilia E. Sukhorukova, Cand. Sci. (Med.), Researcher, Laboratory of Cellular and Molecular Immunology

suhorukova@niigpk.ruhttps://orcid.org/0000-0001-6036-4250ШардаковВ. И.ShardakovV. I.

Шардаков Виктор Иванович, доктор медицинских наук, профессор, ведущий научный сотрудник лаборатории клеточной и молекулярной иммунологии

Viktor I. Shardakov, Dr. Sci. (Med.), Prof., Leading Researcher, Laboratory of Cellular and Molecular Immunology

shardakov@niigpk.ruФГБУН «Кировский научно-исследовательский институт гематологии и переливания крови Федерального медико-биологического агентства»РоссияKirov Research Institute of Hematology and Blood Transfusion of the Federal Medical and Biology Agency of RussiaRussian Federation2019100820196417989Copyright © Назарова Е.Л., Минаева Н.В., Зотина Е.Н., Докшина И.А., Сухорукова Э.Е., Шардаков В.И., 20192019Назарова Е.Л., Минаева Н.В., Зотина Е.Н., Докшина И.А., Сухорукова Э.Е., Шардаков В.И.Nazarova E.L., Minaeva N.V., Zotina E.N., Dokshina I.A., Suhorukova E.E., Shardakov V.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.htjournal.ru/jour/article/view/128Введение

Введение. Режимы терапии с использованием бортезомиба способствовали значительному улучшению выживаемости больных множественной миеломой (ММ), но могут осложняться периферической полинейропатией (ПП).

Цель работы — выявить группу риска развития бортезомиб-индуцированной ПП на основании анализа полиморфизма генов иммунного ответа у больных с впервые диагностированной ММ.

Материалы и методы

Материалы и методы. С использованием подхода выявления генов-кандидатов проведено исследование ассоциации 20 полиморфных локусов 14 генов иммунного ответа у 46 больных MM, получавших терапию VCD, включающую в себя бортезомиб.

Результаты

Результаты. Распределение однонуклеотидных полиморфизмов сравнили в группах больных ММ с наличием и отсутствием ПП. Среди больных с ПП чаще встречались гомозиготные носители аллеля «дикого» типа генов TLR6 (Ser249Pro) (р = 0,006), IL1β (G-1473C) (р = 0,04), IL4 (C-589T) (р = 0,04), а также носители гаплотипов с мутантным аллелем гена IL10 (G-1082A) (р = 0,04) и с аллелем «дикого» типа гена IL2 (T-330G) (р = 0,01).

Заключение

Заключение. Подтвержден вклад генетической компоненты в риск развития бортезомиб-индуцированной нейропатии, что может оказать помощь в персонализации терапии больных ММ.

Background

Background. The regimens of therapy with bortezomib have significantly improved the survival among patients with multiple myeloma (MM). However, the development of peripheral polyneuropathy (PP) resulting from treatment using proteasome inhibitors is still an undesirable event. Risk factors for PP in MM patients include old age, previous neuropathy and use of neurotoxic drugs. Recent studies have established the presence of a genetic component in the mechanism of developing bortezomib-induced neurotoxicity. However, there are conflicting opinions on the role of genetic characteristics in predicting the risk of treatment-induced neuropathy development.

Aim

Aim. To identify the risk group of bortezomib-induced PP based on the analysis of gene polymorphism of the immune response in patients with newly-diagnosed MM.

Materials and methods

Materials and methods. A study of the association of 20 polymorphic loci of 14 immune response genes in 46 MM patients was conducted using a candidate gene identification approach. All the patietns were receiving VCD therapy with bortezomib.

Results

Results. The distribution of single nucleotide polymorphisms was compared in groups of patients with the presence and absence of PP. It is found that homozygous carriers of the wild type allele of the genes TLR6 (Ser249Pro) (p = 0.006), IL1β (G-1473C) (p = 0.04), IL4 (C-589T) (p = 0.04), as well as haplotype carriers with the mutant allele of the gene IL10 (G-1082A) (p = 0.04) and with the wild type allele gene IL2 (T-330G) (p = 0.01) were significantly more frequent among PP patients.

Сonclusion

Сonclusion. Our results have confirmed the contribution of the genetic component to the risk of developing bortezomibinduced neuropathy. These findings can be used for individualization of therapeutic approaches to the treatment of MM patients.

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The authors declare that there are no conflicts of interest present.