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С возрастом во всех тканях увеличивается количество соматических мутаций в генах. Лучше всего этот процесс изучен в гемопоэтических стволовых клетках (ГСК). Некоторые мутации могут привести к пролиферативному преимуществу и экспансии ГСК с образованием клона и развитием клонального гемопоэза (КГ). Клональный гемопоэз неопределенного потенциала (КГНП) характеризуется наличием клона при отсутствии опухолей системы крови. Развитие КГ и КГНП ассоциировано с увеличением риска заболеваний сердечно-сосудистой системы и гематологических неоплазий. Развитию КГ и КГНП способствуют лучевая и химиотерапия, факторы внешней среды. Для старения характерны мутации так называемой группы генов DTА (аббревиатура, образованная первыми буквами генов DNMT3A, ТЕТ2 и ASXL1). При внешних воздействиях (химиотерапия, лучевая терапия, экологические токсины, облучение при космических полетах) чаще мутируют гены, регулирующие ответ на повреждение ДНК — группа DDR (сокращенно от DNA damage response): TP53, PPM1D, BRCC3, CHEK2. В связи с повышенным риском развития злокачественных новообразований, лица с КГ и КГНП нуждаются в динамическом наблюдении.
Библиографические ссылки
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