DNMT3A и ASXL1

Выявление мутаций генов эпигенетической регуляции генома IDH1/2, DNMT3A, ASXL1 и их сочетания с мутациями FLT3, NPM1, RUNX1 у пациентов с острыми миелоидными лейкозами

МИЕЛОИДНЫЕ ОПУХОЛИ , , ,

Е.В. Белоцерковская1,2, Е.К. Зайкова1,2, А.В. Петухов1,2,3, О.Н. Демидов2, К.А. Левчук1, И.Г. Будаева1, Д.В. Зайцев1, Ю.Д. Роговая1, А.А. Шатилова1, К.В. Богданов1, Ю.В. Миролюбова1, Т.С. Никулина1, А.Ю. Зарицкий1, Л.Л. Гиршова1

1 ФГБУ «НМИЦ им. В.А. Алмазова» Минздрава России, ул. Аккуратова, д. 2, Санкт-Петербург, Российская Федерация, 197341

2 ФГБУН «Институт цитологии РАН», Тихорецкий пр-т, д. 4, Санкт-Петербург, Российская Федерация, 194064

3 НТУ «Сириус», Олимпийский пр-т, д. 1, Сочи, Российская Федерация, 354340

Для переписки: Екатерина Васильевна Белоцерковская, канд. биол. наук, ул. Аккуратова, д. 2, Санкт-Петербург, Российская Федерация, 197341; e-mail: belotserkovskaya.ev@gmail.com

Для цитирования: Белоцерковская Е.В., Зайкова Е.К., Петухов А.В. и др. Выявление мутаций генов эпигенетической регуляции генома IDH1/2, DNMT3A, ASXL1 и их сочетания с мутациями FLT3, NPM1, RUNX1 у пациентов с острыми миелоидными лейкозами. Клиническая онкогематология. 2021;14(1):13–21.

DOI: 10.21320/2500-2139-2021-14-1-13-21

РЕФЕРАТ

Цель. Выявление мутаций генов IDH1/IDH2, DNMT3A и ASXL1, ответственных за эпигенетическую регуляцию генома, при впервые диагностированных острых миелоидных лейкозах (ОМЛ) у взрослых и их сочетания с мутациями генов FLT3, NPM1, RUNX1.

Материалы и методы. В исследование включено 56 пациентов с впервые выявленным ОМЛ, проходивших лечение в ФГБУ «НМИЦ им. В.А. Алмазова» Минздрава России. Среди них было 34 мужчины и 22 женщины в возрасте 18–76 лет (медиана 46 лет). Мутационный статус генов эпигенетической регуляции IDH1, IDH2, DNMT3A и ASXL1 определяли методом секвенирования по Сэнгеру. Молекулярно-генетический анализ генов FLT3, NPM1, RUNX1-RUNX1T1 выполняли с использованием коммерческих наборов.

Результаты. Мутации генов эпигенетической регуляции обнаружены у 14 (25 %) из 56 пациентов. Распространенность мутаций не была связана с группами риска (p = 0,072). Мутации IDH1/2 выявлены у 15,6 % пациентов и статистически значимо чаще обнаруживались одновременно с мутациями NPM1 (62,5 %; p = 0,01) по сравнению с пациентами с диким типом IDH1/2. У большинства пациентов мутации IDH1/2 были связаны с нормальным кариотипом (p = 0,002). Мутация DNMT3A (R882) определена у 4 (7,1 %) из 56 пациентов анализируемой группы. У 6 (11,1 %) пациентов были идентифицированы мутации ASXL1, которые сочетались мутациями с RUNX1-RUNX1T1 и FLT3-ITD.

Заключение. Мутации генов эпигенетической регуляции часто обнаруживаются у пациентов с ОМЛ и могут сочетаться с нарушениями в генах NPM1, FLT3 и RUNX1.

Ключевые слова: острые миелоидные лейкозы, гены эпигенетической регуляции IDH1, IDH2, DNMT3A и ASXL1, эпигенетические факторы.

Получено: 20 августа 2020 г.

Принято в печать: 2 декабря 2020 г.

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Статистика Plumx русский

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