SLC7A11/GPX4-зависимая резистентность к индукции ферроптоза в клетках острого миелоидного лейкоза: молекулярные маркёры и терапевтические перспективы

В обзоре представлен анализ современных литературных данных о роли железозависимой регулируемой гибели клеток (ферроптоза) в патогенезе острого миелоидного лейкоза (ОМЛ). Рассмотрены молекулярные механизмы SLC7A11/GPX4-зависимой резистентности лейкозных клеток к индукции ферроптоза, включая транскрипционную регуляцию антиферроптотических генов факторами NRF2, p53, ATF4, а также эпигенетические модификации. Особое внимание уделено роли лейкозных стволовых клеток в поддержании резистентности через активацию альтернативных защитных путей (FSP1–CoQ10, DHODH) и регуляцию гомеостаза железа. Проанализированы экспериментальные данные, полученные на клеточных линиях ОМЛ (HL-60, KG-1, MOLM-13, MV4-11, THP-1), и терапевтические стратегии фармакологической блокады оси SLC7A11–GSH–GPX4 с использованием индукторов ферроптоза (эрастин, RSL3, ML162). Рассмотрены возможности комбинированной терапии с участием таргетных препаратов, гипометилирующих агентов и модуляторов липидного метаболизма. Предложены молекулярные маркёры (SLC7A11, GPX4, ACSL4, FSP1, NRF2, уровень липидной пероксидации) для стратификации пациентов и персонализации терапии резистентных форм ОМЛ.

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