ArticleScience translational medicine2021
ULK1 inhibition promotes oxidative stress-induced differentiation and sensitizes leukemic stem cells to targeted therapy.
Article in Science translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Scientific landscape of oxidative stress in sarcopenia: from bibliometric analysis to hotspots review.Frontiers in medicine · 2024Pooled it
- LDH-mediated autophagic full-chain blockade for Multiple Myeloma treatment by targeting circ_0008255/miR-192-5p/ATG2A axis.Bioactive materials · 2027Article
- Understanding drug resistance in chronic myeloid leukemia through the lens of leukemic stem cell states: insights from single-cell analyses.Haematologica · 2026Review
- Divergent Role of ULK1 to Balance Mitochondrial Homeostasis and Bioenergetics in Ovarian Cancer Spheroids.Cancers · 2026Article
- Targeting Mitochondrial Vulnerabilities in Chronic Myeloid Leukemia: From Pathobiology to Novel Therapeutic Opportunities.Cancers · 2026Review
- Single-cell disentangled representations for perturbation modeling and treatment effect estimation.bioRxiv : the preprint server for biology · 2026Article
- Activating protein kinases to treat diseases: Current understanding and future challenges.Acta pharmaceutica Sinica. B · 2026Review
- Hsp70-Bim interaction mediated mitophagy as a potential therapeutic target for CML stem cells.Stem cell reports · 2026Article
- Autophagy-Lysosome Pathway Dysfunction in Neurodegeneration and Cancer: Mechanisms and Therapeutic Opportunities.International journal of molecular sciences · 2025Review
- Treatment-Free Remission in Chronic Myeloid Leukemia: Revisiting the "W" Questions.European journal of haematology · 2025Review
- Decoding the diagnostic biomarkers of mitochondrial dysfunction related gene variants in pediatric T cell acute lymphoblastic leukemia.Scientific reports · 2025Article
- Mitochondrial quality control in hematopoietic stem cells: mechanisms, implications, and therapeutic opportunities.Stem cell research & therapy · 2025Review
- Autophagy and Cancer: Insights into Molecular Mechanisms and Therapeutic Approaches for Chronic Myeloid Leukemia.Biomolecules · 2025Review
- Loss of Function Mouse Models Reveal a Novel Regulatory Function for ULK1 in Myeloproliferative Neoplasms.Molecular and cellular biology · 2025Article
- Chiglitazar diminishes the warburg effect through PPARγ/mTOR/PKM2 and increases the sensitivity of imatinib in chronic myeloid leukemia.Experimental hematology & oncology · 2024Article
- Tumor Biology Hides Novel Therapeutic Approaches to Diffuse Large B-Cell Lymphoma: A Narrative Review.International journal of molecular sciences · 2024Review
- Leukemia and mitophagy: a novel perspective for understanding oncogenesis and resistance.Annals of hematology · 2024Review
- Inhibition of mitochondrial folate metabolism drives differentiation through mTORC1 mediated purine sensing.Nature communications · 2024Article
- Redox-Responsive Polymeric Nanoparticle for Nucleic Acid Delivery and Cancer Therapy: Progress, Opportunities, and Challenges.Macromolecular bioscience · 2024Review
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Abstract
Inhibition of autophagy has been proposed as a potential therapy for individuals with cancer. However, current lysosomotropic autophagy inhibitors have demonstrated limited efficacy in clinical trials. Therefore, validation of novel specific autophagy inhibitors using robust preclinical models is critical. In chronic myeloid leukemia (CML), minimal residual disease is maintained by persistent leukemic stem cells (LSCs), which drive tyrosine kinase inhibitor (TKI) resistance and patient relapse. Here, we show that deletion of autophagy-inducing kinase ULK1 (unc-51–like autophagy activating kinase 1) reduces growth of cell line and patient-derived xenografted CML cells in mouse models. Using primitive cells, isolated from individuals with CML, we demonstrate that pharmacological inhibition of ULK1 selectively targets CML LSCs ex vivo and in vivo, when combined with TKI treatment. The enhanced TKI sensitivity after ULK1-mediated autophagy inhibition is driven by increased mitochondrial respiration and loss of quiescence and points to oxidative stress–induced differentiation of CML LSCs, proposing an alternative strategy for treating patients with CML.
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