Ferroptosis in Haematological Malignancies: From Regulatory Networks to Novel Therapeutic Opportunities

Abstract

Haematological malignancies encompass a wide spectrum of blood cell disorders with diverse prognoses. Despite recent advances in therapy, many of these disorders remain incurable or exhibit relapse and drug resistance. Ferroptosis, an iron-dependent form of cell death caused by lipid peroxidation, holds promise as a strategy to overcome the resistance seen with conventional therapies. This review aims to succinctly outline current research concerning the regulatory function of ferroptosis-related genes (FRGs) and various types of non-coding RNAs (ncRNAs), as well as various types of ferroptosis inducers (FINs), encompassing small molecule compounds, natural derivatives, synthetic agents and nanoparticles. The exploration delves into the mechanisms by which FINs operate, including inhibiting the system Xc⁻, deactivating the enzyme glutathione peroxidase 4 (GPX4), disrupting glutathione (GSH) production and interfering with iron or lipid metabolism. The investigation emphasises the functioning of these agents and the underlying molecular processes driving the initiation of ferroptosis. A comprehensive assessment reveals the potential utility of FINs as innovative treatments for haematological neoplasms, offering insights into a novel therapeutic approach.