ArticleThe Journal of clinical investigation2009
Targeting autophagy potentiates tyrosine kinase inhibitor-induced cell death in Philadelphia chromosome-positive cells, including primary CML stem cells.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 300 papers.
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
300 citing papers in PubMed, 557 citations in OpenAlex.
- SMAD4 loss is associated with response to neoadjuvant chemotherapy plus hydroxychloroquine in patients with pancreatic adenocarcinoma.Clinical and translational science · 2021Trial
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- Phase II randomized, double-blind, placebo-controlled study of whole-brain irradiation with concomitant chloroquine for brain metastases.Radiation oncology (London, England) · 2013Trial
- Cardio-Oncology in Cold Climates: Epidemiological Features, Bidirectional Interaction Mechanisms, and Integrated Management Strategies.Cardiovascular toxicology · 2026Review
- Oxidative Phosphorylation and Fatty Acid Oxidation Are Central to Mitochondrial Metabolism Rewiring in CML Stem/Progenitor Cell Survival.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026Review
- Review
- Emerging perspectives in proteostasis: bridging mechanisms and therapeutics for human diseases.Signal transduction and targeted therapy · 2026Review
- Article
- Hsp70-Bim interaction mediated mitophagy as a potential therapeutic target for CML stem cells.Stem cell reports · 2026Article
- Targeting Lysosomes for Enhanced Anti-Cancer Therapeutics and Immune Response.International journal of biological sciences · 2026Review
- Targeting autophagy and metabolism for ewing sarcoma.Molecular biology reports · 2025Review
- Lipid Storage and Therapy Resistance in Chronic Myeloid Leukaemia: A Novel Perspective on Targeting Metabolic Vulnerabilities.Cancers · 2025Review
- Review
- Nonreceptor tyrosine kinase ABL1 regulates lysosomal acidification by phosphorylating the ATP6V1B2 subunit of the vacuolar-type HAutophagy · 2025Article
- PTBP2 promotes cell survival and autophagy in chronic myeloid leukemia by stabilizing BNIP3.Cell death & disease · 2025Article
- Review
- Autophagy and Cancer: Insights into Molecular Mechanisms and Therapeutic Approaches for Chronic Myeloid Leukemia.Biomolecules · 2025Review
- Regulation of autophagy by Rab27B in colorectal cancer.The international journal of biochemistry & cell biology · 2024Article
- Current Understanding of the Role of Autophagy in the Treatment of Myeloid Leukemia.International journal of molecular sciences · 2024Review
- Targeting Lipid Metabolism in Cancer Stem Cells for Anticancer Treatment.International journal of molecular sciences · 2024Review
240 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
21 authors at 6 institutions in 3 countries.
Funding
Abstract
Imatinib mesylate (IM), a potent inhibitor of the BCR/ABL tyrosine kinase, has become standard first-line therapy for patients with chronic myeloid leukemia (CML), but the frequency of resistance increases in advancing stages of disease. Elimination of BCR/ABL-dependent intracellular signals triggers apoptosis, but it is unclear whether this activates additional cell survival and/or death pathways. We have shown here that IM induces autophagy in CML blast crisis cell lines, CML primary cells, and p210BCR/ABL-expressing myeloid precursor cells. IM-induced autophagy did not involve c-Abl or Bcl-2 activity but was associated with ER stress and was suppressed by depletion of intracellular Ca2+, suggesting it is mechanistically nonoverlapping with IM-induced apoptosis. We further demonstrated that suppression of autophagy using either pharmacological inhibitors or RNA interference of essential autophagy genes enhanced cell death induced by IM in cell lines and primary CML cells. Critically, the combination of a tyrosine kinase inhibitor (TKI), i.e., IM, nilotinib, or dasatinib, with inhibitors of autophagy resulted in near complete elimination of phenotypically and functionally defined CML stem cells. Together, these findings suggest that autophagy inhibitors may enhance the therapeutic effects of TKIs in the treatment of CML.
Indexed as
Identifiers
What OpenQuestion holds
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 OpenQuestion graph.