ArticleJournal of cellular physiology2019
The Bcl-2 inhibitor venetoclax inhibits Nrf2 antioxidant pathway activation induced by hypomethylating agents in AML.
Article in Journal of cellular physiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Efficacy of 10-day decitabine in acute myeloid leukemia.Leukemia research · 2021Trial
- Nucleolin Alterations and ROS Production Associate With Sensitivity of AML Cells to Venetoclax.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Venetoclax for elderly patients with acute myeloid leukaemia unfit for intensive chemotherapy: Prospects, resistance mechanisms and management strategies.Clinical and translational medicine · 2026Review
- Venetoclax and hypomethylating agents synergize to increase cell death and metabolic remodeling in acute B-lymphoblastic leukemia cells.Molecular metabolism · 2026Article
- Chidamide combined with decitabine, venetoclax, and low-dose cytarabine for relapsed/refractory acute myeloid leukemia: a single-center case series.Frontiers in oncology · 2026Article
- Venetoclax-Based Therapy for Early Relapse in Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation: A Case Report and Minireview.Cancer reports (Hoboken, N.J.) · 2026Review
- Exploring the Co-delivery of Sorafenib and Venetoclax to Induce Ferroptosis and Apoptosis Mediated Cancer Cell Death using Surface Modified PLGA Nanoparticles.AAPS PharmSciTech · 2025Article
- The combination of venetoclax with dimethyl fumarate synergistically induces apoptosis in AML cells by disrupting mitochondrial integrity through ROS accumulation.Cell death & disease · 2025Article
- The Heme Oxygenase/Biliverdin Reductase System as a Therapeutic Target to Counteract Cellular Senescence in Alzheimer's Disease.Antioxidants (Basel, Switzerland) · 2025Review
- Superoxide-mediated phosphorylation and stabilization of Mcl-1 by AKT underlie venetoclax resistance in hematologic malignancies.Leukemia · 2025Article
- Inhibition of FOXM1 Synergizes with BH3 Mimetics Venetoclax and Sonrotoclax in Killing Multiple Myeloma Cells through Repressing MYC Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Targeting Nrf2 in acute myeloid leukemia: an updated review on its role in chemoresistance and emerging therapeutic strategies.Medical oncology (Northwood, London, England) · 2025Review
- Polyamines at the crossroad between cell metabolism and epigenetic regulation in acute leukemias.Cell death discovery · 2025Review
- Unraveling Venetoclax Resistance: Navigating the Future of HMA/Venetoclax-Refractory AML in the Molecular Era.Cancers · 2025Review
- Targeting RNA modification and mitochondrial metabolism cross talk in leukemic stem cells with CDK7 inhibitor TGN-1062.Blood advances · 2025Article
- Targeting epigenetic and post-translational modifications of NRF2: key regulatory factors in disease treatment.Cell death discovery · 2025Review
- Next generation thiazolyl ketone inhibitors of cytosolic phospholipase ANature communications · 2025Article
- Clinical efficacy and safety of venetoclax combined with hypomethylating agents in relapsed high-risk acute myeloid leukemia patients after allogeneic hematopoietic stem cell transplantation.Frontiers in medicine · 2025Article
- Immunomodulatory Effects and Mechanisms of Two-Dimensional Black Phosphorus on Macrophage Polarization and Bone Regeneration.International journal of nanomedicine · 2025Review
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Induction of reactive oxygen species (ROS), an important process for the cytotoxicity of various acute myeloid leukemia (AML) therapies including hypomethylating agents (HMAs), concurrently activates the NF-E2-related factor 2 (Nrf2) antioxidant response pathway which in turn results in induction of antioxidant enzymes that neutralize ROS. In this study, we demonstrated that Nrf2 inhibition is an additional mechanism responsible for the marked antileukemic activity in AML seen with the combination of HMAs and venetoclax (ABT-199). HMA and venetoclax combined treatment augmented mitochondrial ROS induction and apoptosis compared with treatment HMA alone. Treatment of AML cell lines as well as primary AML cells with venetoclax disrupted HMA decitabine-increased nuclear translocation of Nrf2 and induction of downstream antioxidant enzymes including heme oxygenase-1 and NADP-quinone oxidoreductase-1. Venetoclax treatment also leads to dissociation of B-cell lymphoma 2 from the Nrf2/Keap-1 complex and targets Nrf2 to ubiquitination and proteasomal degradation. Thus, our results here demonstrated an undiscovered mechanism underlying synergistic effect of decitabine and venetoclax in AML cells, elucidating for impressive results in antileukemic activity against AML in preclinical and early clinical studies by combined treatment of these drugs.
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