ArticleCell death & disease2021
Nrf2 overexpression increases risk of high tumor mutation burden in acute myeloid leukemia by inhibiting MSH2.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 41 citations in OpenAlex.
- ANXA1 overexpression promotes B cell acute lymphoblastic leukemia progression and resistance by regulating fatty acid metabolism through PI3K/Akt signaling.Molecular and cellular biochemistry · 2026Article
- Nrf2 as a redox checkpoint in autoimmune joint inflammation: microenvironmental redox control across the arthritis spectrum.Frontiers in immunology · 2026Review
- Therapeutic innovations: targeting ROS production in AML with natural and synthetic compounds.Naunyn-Schmiedeberg's archives of pharmacology · 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
- Correlations of phosphorylated Nrf2 with responses to neoadjuvant chemotherapy in patients with triple-negative breast cancer.BMC women's health · 2025Observational
- Review
- The Cancer Antioxidant Regulation System in Therapeutic Resistance.Antioxidants (Basel, Switzerland) · 2024Review
- Inhibition of NRF2 enhances the acute myeloid leukemia cell death induced by venetoclax via the ferroptosis pathway.Cell death discovery · 2024Article
- Roles of NRF2 in DNA damage repair.Cellular oncology (Dordrecht, Netherlands) · 2023Review
- Immune checkpoints represent a promising breakthrough in targeted therapy and prognosis of myelodysplastic syndrome.Heliyon · 2023Review
- Identification of NRF2 Activation as a Prognostic Biomarker in T-Cell Acute Lymphoblastic Leukaemia.International journal of molecular sciences · 2023Article
- A pan-cancer analysis shows immunoevasive characteristics in NRF2 hyperactive squamous malignancies.Redox biology · 2023Article
- Susceptibility of acute myeloid leukemia cells to ferroptosis and evasion strategies.Frontiers in molecular biosciences · 2023Review
- A New Nrf2 Inhibitor Enhances Chemotherapeutic Effects in Glioblastoma Cells Carrying p53 Mutations.Cancers · 2022Article
- Anti-Inflammatory Mechanisms of Dietary Flavones: Tapping into Nature to Control Chronic Inflammation in Obesity and Cancer.International journal of molecular sciences · 2022Review
- Nrf2 overexpression increases the resistance of acute myeloid leukemia to cytarabine by inhibiting replication factor C4.Cancer gene therapy · 2022Article
- DNMT3A R882H mutation drives daunorubicin resistance in acute myeloid leukemia via regulating NRF2/NQO1 pathway.Cell communication and signaling : CCS · 2022Article
- Review
- Targeting PD-1/PD-L1 pathway in myelodysplastic syndromes and acute myeloid leukemia.Experimental hematology & oncology · 2022Review
- Cannabidiol Inhibits Tumorigenesis in Cisplatin-Resistant Non-Small Cell Lung Cancer via TRPV2.Cancers · 2022Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nuclear factor erythroid 2-related factor 2 (Nrf2, also called NFE2L2) plays an important role in cancer chemoresistance. However, little is known about the role of Nrf2 in tumor mutation burden and the effect of Nrf2 in modulating DNA mismatch repair (MMR) gene in acute myeloid leukemia (AML). Here we show that Nrf2 expression is associated with tumor mutation burden in AML. Patients with Nrf2 overexpression had a higher frequency of gene mutation and drug resistance. Nrf2 overexpression protected the AML cells from apoptosis induced by cytarabine in vitro and increased the risk of drug resistance associated with a gene mutation in vivo. Furthermore, Nrf2 overexpression inhibited MutS Homolog 2 (MSH2) protein expression, which caused DNA MMR deficiency. Mechanistically, the inhibition of MSH2 by Nrf2 was in a ROS-independent manner. Further studies showed that an increased activation of JNK/c-Jun signaling in Nrf2 overexpression cells inhibited the expression of the MSH2 protein. Our findings provide evidence that high Nrf2 expression can induce gene instability-dependent drug resistance in AML. This study demonstrates the reason why the high Nrf2 expression leads to the increase of gene mutation frequency in AML, and provides a new strategy for clinical practice.
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