medbioМедико-биологические проблемы жизнедеятельностиMedical and Biological Problems of Life Activity2074-2088Республиканский научно-практический центр радиационной медицины и экологии человека10.58708/2074-2088.2026-3(39)-5-12medbio-539Research ArticleОБЗОРЫ И ПРОБЛЕМНЫЕ СТАТЬИREVIEWS AND PROBLEM ARTICLESSLC7A11/GPX4-зависимая резистентность к индукции ферроптоза в клетках острого миелоидного лейкоза: молекулярные маркёры и терапевтические перспективыSLC7A11/GPX4-dependent resistance to ferroptosis induction in acute myeloid leukemia cells: molecular markers and therapeutic prospectshttps://orcid.org/0009-0004-6688-0829ГельдымамедовЧ. А.GeldimammedovC. A.

г. Гомель

profgeldimamedov@gmail.comhttps://orcid.org/0000-0002-0797-6554КовальА. Н.KovalA. N.

г. Гомель

akovalj@ya.ruhttps://orcid.org/0009-0004-9586-0034ЛитвинчукА. В.LitvinchukA V.

г. Гомель

litvinalexa@gmail.comhttps://orcid.org/0009-0009-8284-8980ШпудейкоВ. К.ShpudeikoV. K.

г. Гомель

victorshpudeiko@gmail.comhttps://orcid.org/0009-0006-0143-243XПуртоваК. А.PurtovaK. A.

г. Гомель

purtovaka01@mail.ruМедицинский центр «Сальфирина»BelarusУО «Гомельский государственный медицинский университет»BelarusГУ «РНПЦ радиационной медицины и экологии человека»Belarus20260111202603512Copyright © Гельдымамедов Ч.А., Коваль А.Н., Литвинчук А.В., Шпудейко В.К., Пуртова К.А., 20262026Гельдымамедов Ч.А., Коваль А.Н., Литвинчук А.В., Шпудейко В.К., Пуртова К.А.Geldimammedov C.A., Koval A.N., Litvinchuk A.V., Shpudeiko V.K., Purtova K.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://medbio.ejournal.by/jour/article/view/539

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.

The review presents an analysis of current literature data on the role of iron-dependent regulated cell death (ferroptosis) in the pathogenesis of acute myeloid leukemia (AML). The molecular mechanisms of SLC7A11/GPX4-dependent resistance of leukemic cells to ferroptosis induction are discussed, including transcriptional regulation of anti-ferroptotic genes by NRF2, p53, ATF4 factors, as well as epigenetic modifications. Special attention is paid to the role of leukemic stem cells in maintaining resistance through activation of alternative defense pathways (FSP1–CoQ10, DHODH) and regulation of iron homeostasis. Experimental data obtained on AML cell lines (HL-60, KG-1, MOLM-13, MV4-11, THP-1) and therapeutic strategies for pharmacological blockade of the SLC7A11–GSH–GPX4 axis using ferroptosis inducers (erastin, RSL3, ML162) are analyzed. The prospects of combination therapy with targeted drugs, hypomethylating agents, and lipid metabolism modulators are discussed. Molecular markers (SLC7A11, GPX4, ACSL4, FSP1, NRF2, lipid peroxidation level) for patient stratification and personalization of treatment for resistant forms of AML are highlighted.

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The authors declare that there are no conflicts of interest present.