Феномен клонального гемопоэза: этиология, классификация и прогностическая роль

   Феномен клонального гемопоэза (КГ) стал объектом интенсивных исследований с 2014 г., чему способствовало развитие технологии высокопроизводительного секвенирования. С возрастом увеличивается распространенность КГ, который связан с повышенным риском онкогематологических и сердечно‑сосудистых заболеваний, а также общей летальностью. Возникновение соматических мутаций в гемопоэтических стволовых клетках является основным механизмом КГ, в результате которого нарушается баланс между клеточным делением и дифференцировкой, что приводит к экспансии клонов клеток с определенными генетическими изменениями. В статье рассматривается понятие КГ и его различных форм, включая КГ неопределенного и онкогенного потенциала, а также связанные состояния, такие как идиопатическая цитопения неопределенного значения, клональная цитопения неопределенного значения и идиопатическая дисплазия неопределенного значения. КГ определяют при наличии соматических мутаций в генах миелоидной направленности (наиболее часто – DNMT3A, TET2 и ASXL1) в кроветворных клетках, которые могут присутствовать как у здоровых людей, так и у пациентов с гематологическими неоплазиями. Подчеркнута важность разграничения различных форм КГ в зависимости от их прогностической значимости и потенциального риска трансформации в злокачественные новообразования. Мутации, связанные с КГ, могут увеличивать риск сердечно‑сосудистых заболеваний, сахарного диабета 2‑го типа, хронической обструктивной болезни легких, венозных тромбозов, а также миелоидных и лимфоидных новообразований. Отмечена необходимость разработки формализованных диагностических критериев и прогностических моделей для стратификации риска у лиц с различными формами КГ, что может значительно повлиять на подходы к диагностике и возможность терапии данных состояний.

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