ArticleExperimental hematology & oncology2023
Targeting NRF2 uncovered an intrinsic susceptibility of acute myeloid leukemia cells to ferroptosis.
Article in Experimental hematology & oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 51 citations in OpenAlex.
- Ferroptosis-related genes influence AML risk through immune cell-mediated pathways: a Mendelian randomization study with mediation analysis.Blood research · 2026Article
- Recent advancements in NRF2-regulated ferroptosis modulation for targeted cancer therapy.Molecular biology reports · 2026Review
- Selenoprotein thioredoxin reductase 1 promotes cancer cells ferroptosis by suppressing GPX4 expression.Cell death and differentiation · 2026Article
- Targeting Hippocampal PTEN Suppresses Ferroptosis and Rescues Cognitive Decline in Alzheimer's Disease via Dual AKT/GSK3β/Nrf2 and AKT/STAT3 Axes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- From complexity to clarity: aging bone marrow niche in bone and blood regeneration and malignancy.Bone research · 2026Review
- Dual targeting of GPX4 and TXNRD1 triggers eradication of AML cells through induction of apoptosis and ferroptosis.Experimental hematology & oncology · 2026Article
- METTL16 in cancer: Roles and regulatory mechanisms.Genes & diseases · 2026Review
- Transcriptomic Analysis Reveals an NRF2-Mediated Redox and Metabolic Reprogramming in Sorafenib-Resistant Hepatocellular Carcinoma Cells.Biotech (Basel (Switzerland)) · 2026Article
- Harnessing ferroptosis for cancer therapy: Mechanisms and therapeutic strategies (Review).Oncology reports · 2026Review
- Regulating Ferroptosis in Leukemic Stem Cells: From Stemness Preservation to Targeted Differentiation Strategies.Stem cell reviews and reports · 2026Review
- Ferroptosis in hematological malignancies: molecular mechanisms and therapeutic potential.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Ferroptosis in AML: nanoparticles, biomarkers, and immune rewiring for therapeutic breakthroughs.Discover oncology · 2025Review
- Targeting Nrf2 in acute myeloid leukemia: an updated review on its role in chemoresistance and emerging therapeutic strategies.Medical oncology (Northwood, London, England) · 2025Review
- The ALDH2/PolG2 axis enhances mitochondrial biogenesis via transcriptional regulation of Nrf2 and promotes chemotherapy resistance in acute myeloid leukaemia.Cell death & disease · 2025Article
- Ferroptosis: a novel therapeutic warrior in the battle against leukemia.Apoptosis : an international journal on programmed cell death · 2025Review
- Targeting the Keap1/Nrf2 axis in cancer: molecular mechanisms and pharmacological interventions.Investigational new drugs · 2025Review
- NRF2 maintains redox balance via ME1 and NRF2 inhibitor synergizes with venetoclax in NPM1-mutated acute myeloid leukemia.Cancer & metabolism · 2025Article
- Latency-Associated Nuclear Antigen (LANA) Promotes Ferroptosis by Suppressing Nrf2/GPX4 and Upregulating MDM2.Pathogens (Basel, Switzerland) · 2025Article
- Ferritin in Acute Myeloid Leukemia: Not Only a Marker of Inflammation and Iron Overload, but Also a Regulator of Cellular Iron Metabolism, Signaling and Communication.International journal of molecular sciences · 2025Review
- Review
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
Drug resistance and poor treatment response are major obstacles to the effective treatment of acute myeloid leukemia (AML). A deeper understanding of the mechanisms regulating drug resistance and response genes in AML is therefore urgently needed. Our previous research has highlighted the important role of nuclear factor E2-related factor 2 (NRF2) in AML, where it plays a critical role in detoxifying reactive oxygen species and influencing sensitivity to chemotherapy. In this study, we identify a core set of direct NRF2 targets that are involved in ferroptosis, a novel form of cell death. Of particular interest, we find that glutathione peroxidase 4 (GPX4) is a key ferroptosis gene that is consistently upregulated in AML, and high expression of GPX4 is associated with poor prognosis for AML patients. Importantly, simultaneous inhibition of NRF2 with ML385 and GPX4 with FIN56 or RSL3 synergistically targets AML cells, triggering ferroptosis. Treatment with ML385 + FIN56/RSL3 resulted in a marked reduction in NRF2 and GPX4 expression. Furthermore, NRF2 knockdown enhanced the sensitivity of AML cells to the ferroptosis inducers. Taken together, our results suggest that combination therapy targeting both NRF2 and GPX4 may represent a promising approach for the treatment of AML.
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