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- Title
Deferasirox Causes Leukaemia Cell Death through Nrf2-Induced Ferroptosis.
- Authors
Hsu, Wan-Yi; Wang, Li-Ting; Lin, Pei-Chin; Liao, Yu-Mei; Hsu, Shih-Hsien; Chiou, Shyh-Shin
- Abstract
Acute lymphoblastic leukaemia (ALL) is the most prevalent cancer in children, and excessive iron buildup resulting from blood transfusions and chemotherapy potentially has a negative impact on treatment outcomes and prognosis in patients with ALL. Therefore, initiating early iron chelation therapy during ALL treatment is a logical approach. Ideally, the selected iron chelator should also possess anti-leukaemia properties. The aim of the present study was to explore the potential impact and underlying mechanism of deferasirox (DFX) in ALL therapy. This study proved that DFX, an iron chelator, is capable of inducing leukaemia cell death through ferroptosis, which is achievable by increasing the expression of acetylated nuclear factor erythroid 2-related factor 2 (NRF2). More specifically, NRF2 acetylation on Lys599 was facilitated by acetyltransferase-p300/CBP. These findings indicate that DFX could serve as a potent adjunctive medication for patients with ALL. Moreover, DFX may offer dual benefits in ALL treatment, functioning as both an iron chelator and NRF2-modulating agent. Further research and clinical trials are necessary to fully elucidate the therapeutic potential of DFX in patients with ALL and incorporate it into treatment protocols.
- Subjects
NUCLEAR factor E2 related factor; CELL death; IRON chelates; DEFERASIROX; LEUKEMIA
- Publication
Antioxidants, 2024, Vol 13, Issue 4, p424
- ISSN
2076-3921
- Publication type
Article
- DOI
10.3390/antiox13040424