oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2024-23-1-75-86oncotomsk-2961Research ArticleЛАБОРАТОРНЫЕ И ЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯLABORATORY AND EXPERIMENTAL STUDIESmiR-155 и miR-223 как маркеры клинических особенностей течения хронического лимфолейкозаmiR-155 and miR-223 as markers of biological and clinical features of chronic lymphocytic leukemiahttps://orcid.org/0000-0001-5791-3714ПерепечаеваМ. Л.PerepechaevaM. L.

Перепечаева Мария Леонидовна - кандидат биологических наук, старший научный сотрудник.

630117, Новосибирск, ул. Тимакова, 2/12

Researcher ID (WOS): AAG-1840-2020; Author ID (Scopus): 8283410900

Maria L. Perepechaeva - PhD, Senior Researcher, Institute of Molecular Biology and Biophysics, Federal Research Center for Fundamental and Translational Medicine.

2/12, Timakova St., Novosibirsk, 630117

Researcher ID (WOS): AAG-1840-2020; Author ID (Scopus): 8283410900

mlperepechaeva@frcftm.ruhttps://orcid.org/0000-0002-8129-9176ГореваО. Б.GorevaO. B.

Горева Ольга Борисовна - кандидат биологических наук, старший научный сотрудник.

630117, Новосибирск, ул. Тимакова, 2/12

Researcher ID (WOS): K-3428-2013; Author ID (Scopus): 8691755700

Olga B. Goreva - PhD, Senior Researcher, Institute of Molecular Biology and Biophysics, Federal Research Center for Fundamental and Translational Medicine.

2/12, Timakova St., Novosibirsk, 630117

Researcher ID (WOS): K-3428-2013; Author ID (Scopus): 8691755700

https://orcid.org/0000-0003-0396-3403БерезинаО. В.BerezinaO. V.

Березина Ольга Валерьевна - кандидат медицинских наук, ассистент кафедры терапии, гематологии и трансфузиологии ФПК и ППВ.

630091, Новосибирск, Красный пр., 52

Olga V. Berezina - MD, PhD, Assistant, Department of Therapy, Haematology and Transfusiology of the FPC and PPV, Novosibirsk State Medical University of the Ministry of Health of Russia.

52, Krasny Ave., Novosibirsk, 630091

https://orcid.org/0000-0001-6791-0314ПоспеловаТ. И.PospelovaT. I.

Поспелова Татьяна Ивановна - доктор медицинских наук, профессор, заведующая кафедрой терапии, гематологии и трансфузиологии ФПК и ППВ.

630091, Новосибирск, Красный пр., 52

Author ID (Scopus): 7005792562

Tatiana I. Pospelova - MD, Professor, Head of the Department of Therapy, Haematology and Transfusiology of the FPC and PPV, Novosibirsk State Medical University of the Ministry of Health of Russia.

52, Krasny Ave., Novosibirsk, 630091

Author ID (Scopus): 7005792562

https://orcid.org/0000-0002-5894-1159ГришановаА. Ю.GrishanovaA. Yu.

Гришанова Алевтина Юрьевна - доктор биологических наук, профессор, главный научный сотрудник, заведующая лабораторией чужеродных соединений.

630117, Новосибирск, ул. Тимакова, 2/12

Researcher ID (WOS): C-1759-2014; Author ID (Scopus): 7004298657

Alevtina Yu. Grishanova - Professor, Chief Researcher, Head of the Laboratory of Alien Compounds, Institute of Molecular Biology and Biophysics, Federal Research Center for Fundamental and Translational Medicine.

2/12, Timakova St., Novosibirsk, 630117

Researcher ID (WOS): C-1759-2014. Author ID (Scopus): 7004298657

Научно-исследовательский институт молекулярной биологии и биофизики, ФГБНУ «Федеральный исследовательский центр фундаментальной и трансляционной медицины»РоссияInstitute of Molecular Biology and Biophysics, Federal Research Center for Fundamental and Translational MedicineRussian FederationФГБОУ ВО «Новосибирский государственный медицинский университет» Минздрава РоссииРоссияNovosibirsk State Medical University of the Ministry of Health of RussiaRussian Federation2024220320242317586Copyright © Перепечаева М.Л., Горева О.Б., Березина О.В., Поспелова Т.И., Гришанова А.Ю., 20242024Перепечаева М.Л., Горева О.Б., Березина О.В., Поспелова Т.И., Гришанова А.Ю.Perepechaeva M.L., Goreva O.B., Berezina O.V., Pospelova T.I., Grishanova A.Y.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.siboncoj.ru/jour/article/view/2961

Введение. Хронический лимфолейкоз (ХЛЛ) – заболевание, которое характеризуется высокой межиндивидуальной гетерогенностью как клинического течения, так и молекулярных паттернов экспрессии генов и регуляторных РНК, способных оказывать влияние на патологический процесс. Вовлеченность регуляторных miR-155 и miR-223 в патогенез ХЛЛ в целом известна, но информации о возможных колебаниях экспрессии miR-155 и miR-223 в зависимости от динамики развития патологического процесса и характеристик врачебного вмешательства недостаточно. Цель исследования – изучение уровня экспрессии miR-155 и miR-223 у больных ХЛЛ с разными биологическими, клиническими особенностями и характеристиками проводимой терапии в субстратах периферической крови: плазме, лимфоцитах, внеклеточных везикулах, а также в костном мозге. Материал и методы. При выполнении работы использовались образцы периферической крови и костного мозга 38 пациентов с диагнозом ХЛЛ из Городского гематологического центра ГБУЗ Новосибирской области «Городская клиническая больница № 2» с 2016 по 2017 г. Оценка уровня экспрессии miR-155 и miR-223 проводилась методом ОТ-ПЦР в реальном времени по принципу TaqMan. Оценку значимости различий групп проводили с помощью непараметрического критерия Манна–Уитни либо непараметрического критерия Краскела–Уоллиса с последующим попарным сравнением с помощью критерия Манна–Уитни. Результаты. Выявлена высокая гетерогенность исследуемых показателей. Анализ продемонстрировал сниженный уровень экспрессии miR-155 и miR-223 в микровезикулах у больных с неблагоприятными хромосомными аберрациями в сравнении с пациентами с хромосомными нарушениями или нормальным кариотипом, ассоциированными с промежуточным влиянием на прогноз ХЛЛ, а также повышенный уровень miR-223 в лимфоцитах периферической крови нелеченых больных ХЛЛ по сравнению с лечеными пациентами. Заключение. Выявлены различия уровня экспрессии miR-155 и miR-223 в зависимости от хромосомных аберраций и проведения полихимиотерапии. Полученные предварительные итоги являются заделом для последующих более крупных исследований уровней miR у пациентов с ХЛЛ в зависимости от особенностей течения и лечения заболевания.

Introduction. Chronic lymphocytic leukemia (CLL) is a disease characterized by large individual differences both in the clinical course and in molecular patterns of expression of genes and regulatory RNAs, which can influence pathological changes. The involvement of regulatory microRNAs miR-155 and miR-223 in the pathogenesis of CLL is fairly well known, but there is insufficient information about possible fluctuations in the expression of miR-155 and miR-223 depending on the time course of pathology development and on parameters of medical treatment. Purpose – to investigate the expression of miR-155 and miR-223 in patients having CLL with different biological and clinical features and different characteristics of treatment in terms of peripheral-blood substrates (plasma, lymphocytes, and extracellular vesicles) and bone marrow. Material and Methods. This work involved samples of peripheral blood and bone marrow from 38 patients with a diagnosis of CLL from the City Hematology Center at the government-funded healthcare institution (Novosibirsk Oblast) City Clinical Hospital No. 2 from the years 2016 to 2017. Assessment of miR-155 and miR-223 expressions was carried out by reverse-transcription real-time PCR according to the TaqMan principle. Significance of differences between groups was evaluated either by the nonparametric Mann–Whitney test or by the nonparametric Kruskal–Wallis test with subsequent pairwise comparisons via the Mann–Whitney test. Results. High variation of the analyzed parameters was found. The expression levels of miR-155 and miR-223 in microvesicles of patients with unfavorable chromosomal anomalies were lower than those in patients with the chromosomal aberrations (or the normal karyotype) associated with a moderate effect on CLL prognosis. The expression level of miR-223 in peripheral blood lymphocytes of untreated patients with CLL was higher than that observed in treated patients. Conclusion. differences in the expression levels of miR-155 and miR-223 were identified depending on chromosomal aberrations and polychemotherapy. Our preliminary results will provide the basis for future larger studies on levels of microRNAs in CLL patients having specific features of the development, clinical course, and treatment of the disease.

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