ArticleAntioxidants (Basel, Switzerland)2022
Targeting the NRF2/HO-1 Antioxidant Pathway in FLT3-ITD-Positive AML Enhances Therapy Efficacy.
Article in Antioxidants (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 53 citations in OpenAlex.
- Heme oxygenase-1 in thyroid cancer: a context-dependent regulator.Journal of endocrinological investigation · 2026Review
- HO-1-driven drug resistance in hematological malignancies: Mechanistic insights and advances in targeted therapy.iScience · 2026Review
- Marrow leptin-LEPR signaling rewires mitochondrial oxidative metabolism to confer chemoresistance in acute myeloid leukemia.Cell death & disease · 2026Article
- CD71-Targeted and ROS-Responsive Micelles for Homoharringtonine Delivery to Enhance Therapeutic Efficiency Against FLT3-ITD Acute Myeloid Leukemia.International journal of nanomedicine · 2026Article
- The role of resveratrol in male spermatogenesis: mechanisms and latest advances in clinical applications.Journal of assisted reproduction and genetics · 2025Review
- Mitochondrial Dysfunction in Apoptosis-Resistant Acute Myeloid Leukemia Cells During a Sterile Inflammatory Response.Biomolecules · 2025Article
- Ferroptosis in AML: nanoparticles, biomarkers, and immune rewiring for therapeutic breakthroughs.Discover oncology · 2025Review
- Metabolic Signature ofJournal of personalized medicine · 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
- NRF2 maintains redox balance via ME1 and NRF2 inhibitor synergizes with venetoclax in NPM1-mutated acute myeloid leukemia.Cancer & metabolism · 2025Article
- Navigating heme pathways: the breach of heme oxygenase and hemin in breast cancer.Molecular and cellular biochemistry · 2025Review
- Antileukemia efficacy of the dual BCL2/BCL-XL inhibitor AZD0466 in acute lymphoblastic leukemia preclinical models.Blood advances · 2025Article
- Association of long non-coding RNAs and ABO blood groups with acute lymphoblastic leukemia in Egyptian children.Non-coding RNA research · 2024Article
- Oxidative stress is two-sided in the treatment of acute myeloid leukemia.Cancer medicine · 2024Review
- CLPs-miR-103a-2-5p inhibits proliferation and promotes cell apoptosis in AML cells by targeting LILRB3 and Nrf2/HO-1 axis, regulating CD8 + T cell response.Journal of translational medicine · 2024Article
- Roles of Glutathione and AP-1 in the Enhancement of Vitamin D-Induced Differentiation by Activators of the Nrf2 Signaling Pathway in Acute Myeloid Leukemia Cells.International journal of molecular sciences · 2024Article
- Inhibition of NRF2 enhances the acute myeloid leukemia cell death induced by venetoclax via the ferroptosis pathway.Cell death discovery · 2024Article
- Preparation, structural property, and antioxidant activities of a novel pectin polysaccharide from the flowers ofFrontiers in nutrition · 2024Article
- Cigarette smoke exposure accelerates AML progression in FLT3-ITD models.Blood advances · 2023Article
- Identification of theACS omega · 2023Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute myeloid leukemia (AML) is a molecularly heterogenous hematological malignancy, with one of the most common mutations being internal tandem duplication (ITD) of the juxtamembrane domain of the fms-like tyrosine kinase receptor-3 (FLT3). Despite the development of FLT3-directed tyrosine kinase inhibitors (TKI), relapse and resistance are problematic, requiring improved strategies. In both patient samples and cell lines, FLT3-ITD raises levels of reactive oxygen species (ROS) and elicits an antioxidant response which is linked to chemoresistance broadly in AML. NF-E2-related factor 2 (NRF2) is a transcription factor regulating the antioxidant response including heme oxygenase -1 (HO-1), a heat shock protein implicated in AML resistance. Here, we demonstrate that HO-1 is elevated in FLT3-ITD-bearing cells compared to FLT3-wild type (WT). Transient knockdown or inhibitor-based suppression of HO-1 enhances vulnerability to the TKI, quizartinib, in both TKI-resistant and sensitive primary AML and cell line models. NRF2 suppression (genetically or pharmacologically using brusatol) results in decreased HO-1, suggesting that TKI-resistance is dependent on an active NRF2-driven pathway. In AML-patient derived xenograft (PDX) models, brusatol, in combination with daunorubicin, reduces leukemia burden and prolongs survival. Cumulatively, these data encourage further development of brusatol and NRF2 inhibition as components of combination therapy for refractory AML.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.