Молекулярный мониторинг уровня транскрипта RUNX1-RUNX1T1 при острых миелобластных лейкозах на фоне терапии

Л.Л. Гиршова, Е.Г. Овсянникова, С.О. Кузин, Е.Н. Горюнова, Р.И. Вабищевич, А.В. Петров, Д.В. Моторин, Д.В. Бабенецкая, В.В. Иванов, К.В. Богданов, И.В. Холопова, Т.С. Никулина, Ю.В. Миролюбова, Ю.А. Алексеева, А.Ю. Зарицкий

ФГБУ «Северо-Западный федеральный медицинский исследовательский центр им. В.А. Алмазова» Минздрава России, ул. Аккуратова, д. 2, Санкт-Петербург, Российская Федерация, 197341

Для переписки: Екатерина Геннадьевна Овсянникова, ул. Аккуратова, д. 2, Санкт-Петербург, Российская Федерация, 197341; тел.: +7(921)313-68-35; e-mail: katrin51297@mail.ru

Для цитирования: Гиршова Л.Л., Овсянникова Е.Г., Кузин С.О. и др. Молекулярный мониторинг уровня транскрипта RUNX1-RUNX1T1 при острых миелобластных лейкозов на фоне терапии. Клиническая онкогематология. 2016;9(4):456–64.

DOI: 10.21320/2500-2139-2016-9-4-456-464


РЕФЕРАТ

Актуальность. Современные подходы к терапии острых миелобластных лейкозов (ОМЛ) заключаются в достижении максимальной редукции опухоли и, соответственно, эрадикации лейкозного клона. За исключением случаев изолированной молекулярной перестройки RUNX1-RUNX1T1, целью терапии является достижение неопределяемого уровня таргетного (исследуемого) гена.

Цель. Оценить динамику уровня RUNX1-RUNX1T1 и соответствующих клинических проявлений в ходе мониторинга на различных этапах программной терапии и после ее завершения.

Методы. В работе представлено описание 10 наблюдений ОМЛ с изолированной экспрессией RUNX1-RUNX1T1 (n = 4) и в сочетании с различными молекулярными и цитогенетическими аномалиями (n = 6). Кроме того, представлено наблюдение длительного мониторинга экспрессии гена методом количественного определения RUNX1-RUNX1T1 с помощью ПЦР в реальном времени.

Результаты. Частота рецидивов в группе со снижением уровня экспрессии RUNX1-RUNX1T1 ³ 2 log составила 75 % в сравнении с пациентами, у которых был меньше уровень снижения транскрипта с частотой рецидивов 0 % (= 0,05). Нарастание уровня RUNX1-RUNX1T1 на фоне сохранения костномозговой ремиссии более чем на 1 log совпадало с развитием костномозгового рецидива в течение 5–18 нед. Кроме того, возможно длительное сохранение определенного уровня транскрипта после завершения программной терапии без развития рецидивов.

Заключение. В работе подвергнуты анализу возможные молекулярные предпосылки различных клинических исходов ОМЛ у больных с длительной персистенцией транскрипта RUNX1-RUNX1T1. Это, возможно, позволит сформировать индивидуализированный подход к пациентам с ОМЛ.


Ключевые слова: острый миелобластный лейкоз, ОМЛ, RUNX1-RUNX1T1, молекулярный мониторинг.

Получено: 5 апреля 2016 г.

Принято в печать: 18 апреля 2016 г.

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