ArticleAntioxidants (Basel, Switzerland)2022
Venetoclax-Resistant MV4-11 Leukemic Cells Activate PI3K/AKT Pathway for Metabolic Reprogramming and Redox Adaptation for Survival.
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 24 papers.
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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.
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Who cites it
24 citing papers in PubMed, 25 citations in OpenAlex.
- Results of a phase 1 trial testing ruxolitinib plus venetoclax in patients with relapsed/refractory acute myeloid leukemia.Blood neoplasia · 2026Trial
- Brusatol Triggers Cell Cycle Arrest and Apoptosis, Disrupts Sterol Biosynthesis, and Enhances the Anti-Leukemic Activity of Venetoclax in AML Cells.Cell biochemistry and biophysics · 2026Article
- PI3Kδ inhibitor YY‑20394 is effective alone or in combination with Bcl‑2 inhibitor ABT199 in acute myeloid leukemia cells.Oncology reports · 2026Article
- Combined inhibition of DOT1L and BCL-2 induces synergistic anti-leukemic effects in MLL-rearranged acute myeloid leukemia via suppression of the PI3K/AKT pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Synergistic targeting of eIF4A-mediated translation initiation and apoptosis in acute myeloid leukemia.Blood neoplasia · 2026Article
- Novel NSAID Analogs Exhibit Anti-Leukemic Activity Through Modulation of Apoptotic and Survival Pathways.International journal of molecular sciences · 2026Article
- CHRNB4-Mediated Neuroactive Signaling Rewiring Drives Adaptive Resistance to BCL-2 Inhibition in Acute Myeloid Leukemia.Cancers · 2026Article
- Targeting signaling pathways in lymphoma: From molecular mechanisms to clinical breakthroughs.Chinese medical journal · 2026Review
- Antibacterial activity of bioactive anthraquinones isolated from Cassia tora L. against pathogenic intestinal microorganisms.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Resistance to Targeted Therapy in AML: Current Challenges and Emerging Treatment Strategies.Journal of clinical medicine · 2026Review
- Rewired Neuroactive Ligand-Receptor Signaling Confers Adaptive Resistance to BCL-2 Inhibition in AML.Research square · 2026Article
- NaCells · 2025Article
- Prognostic and immunological characterization of elderly acute myeloid leukemia evaluated by butyrate metabolism-related genes.Discover oncology · 2025Article
- Superoxide-mediated phosphorylation and stabilization of Mcl-1 by AKT underlie venetoclax resistance in hematologic malignancies.Leukemia · 2025Article
- Article
- Tetrahydrobenzimidazole TMQ0153 targets OPA1 and restores drug sensitivity in AML via ROS-induced mitochondrial metabolic reprogramming.Journal of experimental & clinical cancer research : CR · 2025Article
- Lysine-Rich Polypeptide Modulates Forkhead Box O3 and Phosphoinositide 3-Kinase-Protein Kinase B Pathway To Induce Apoptosis in Breast Cancer.ACS pharmacology & translational science · 2024Article
- Disarib, a Specific BCL2 Inhibitor, Induces Apoptosis in Triple-Negative Breast Cancer Cells and Impedes Tumour Progression in Xenografts by Altering Mitochondria-Associated Processes.International journal of molecular sciences · 2024Article
- Extracellular matrix detached cancer cells resist oxidative stress by increasing histone demethylase KDM6 activity.Saudi journal of biological sciences · 2024Article
- The roles of phosphorylation of signaling proteins in the prognosis of acute myeloid leukemia.Pathology oncology research : POR · 2024Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Venetoclax (ABT199) is a selective B-cell lymphoma 2 (BCL-2) inhibitor. The US FDA recently approved it to be used in combination with low-dose cytarabine or hypomethylating agents in acute myeloid leukemia (AML) or elderly patients non-eligible for chemotherapy. However, acquiring resistance to venetoclax in AML patients is the primary cause of treatment failure. To understand the molecular mechanisms inherent in the resistance to BCL-2 inhibitors, we generated a venetoclax-resistant cell line model and assessed the consequences of this resistance on its metabolic pathways. Untargeted metabolomics data displayed a notable impact of resistance on the PI3K/AKT pathway, the Warburg effect, glycolysis, the TCA cycle, and redox metabolism. The resistant cells showed increased NADPH and reduced glutathione levels, switching their energy metabolism towards glycolysis. PI3K/AKT pathway inhibition shifted resistant cells towards oxidative phosphorylation (OXPHOS). Our results provide a metabolic map of resistant cells that can be used to design novel metabolic targets to challenge venetoclax resistance in AML.
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Registered trials
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.