ArticleOncogene2010
Imatinib resistance associated with BCR-ABL upregulation is dependent on HIF-1alpha-induced metabolic reprograming.
Article in Oncogene, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers, 1 of them a synthesis that pooled it.
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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
112 citing papers in PubMed, 1 synthesis or guideline pooled it, 176 citations in OpenAlex.
- Targeting Mitochondrial Oxidative Phosphorylation Eradicates Acute Myeloid Leukemic Stem Cells.Frontiers in oncology · 2022Pooled it
- Modulating metabolic signatures to mitigate cabozantinib resistance in FLT3-ITD acute myeloid leukemia cell models.Cell death discovery · 2026Article
- Machine learning-driven glycolytic subtyping and exosome-based PKM splicing modulation overcome drug resistance in hyper-glycolytic myeloid leukemia.NPJ digital medicine · 2025Article
- Uridine as a hub in cancer metabolism and RNA biology.Experimental & molecular medicine · 2025Review
- Inflammation via JAK-STAT/HIF-1α Drives Metabolic Changes in Pentose Phosphate Pathway and Glycolysis That Support Aortic Valve Cell Calcification.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Unraveling exosome-mediated cancer therapy resistance: pathways and therapeutic challenges.Journal of the Egyptian National Cancer Institute · 2025Review
- Dysregulation of sphingolipid metabolism contributes to the pathogenesis of chronic myeloid leukemia.Cell death & disease · 2025Article
- Chaetocin, a Natural Inhibitor of Transketolase, Suppresses the Non-Oxidative Pentose Phosphate Pathway and Inhibits the Growth of Drug-Resistant Non-Small Cell Lung Cancer.Antioxidants (Basel, Switzerland) · 2025Article
- Hypoxia and activation of hypoxia inducible factor alpha as influencers of inflammatory helper T cells in autoimmune disease - a link between cancer and autoimmunity.Frontiers in immunology · 2025Review
- Targeting hypoxia-inducible factor 1α in chronic graft-versus-host disease to enhance graft-versus-leukemia responses: implications for nanotherapeutics.Frontiers in immunology · 2025Review
- The role of transketolase in the immunotherapy and prognosis of hepatocellular carcinoma: a multi-omics approach.Frontiers in immunology · 2025Article
- Regulation of Hypoxia Dependent Reprogramming of Cancer Metabolism: Role of HIF-1 and Its Potential Therapeutic Implications in Leukemia.Asian Pacific journal of cancer prevention : APJCP · 2024Review
- Associations between HIFs and tumor immune checkpoints: mechanism and therapy.Discover oncology · 2024Review
- HIF-1α signaling: Essential roles in tumorigenesis and implications in targeted therapies.Genes & diseases · 2024Review
- Extraordinary therapeutic effect of PSMA radioligand therapy in treatment-refractory progressive metastatic prostate cancer with the transketolase inhibitor benfo-oxythiamine as a radiosensitizer-A case report.Frontiers in medicine · 2024Article
- Stem cell factor modulates HIF-1α levels and diminishes 5-FU sensitivity in 5-FU resistant pancreatic cells by altering the anabolic glucose metabolism.Journal of biochemical and molecular toxicology · 2023Article
- Article
- Secretory MPP3 reinforce myeloid differentiation trajectory and amplify myeloid cell production.The Journal of experimental medicine · 2023 · on this mapArticle
- The pentose phosphate pathway in health and disease.Nature metabolism · 2023Review
- Review
52 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
Abstract
As chronic myeloid leukemia (CML) progresses from the chronic phase to blast crisis, the levels of BCR-ABL increase. In addition, blast-transformed leukemic cells display enhanced resistance to imatinib in the absence of BCR-ABL-resistance mutations. In this study, we show that when BCR-ABL-transformed cell lines were selected for imatinib resistance in vitro, the cells that grew out displayed a higher BCR-ABL expression comparable to the increase seen in accelerated forms of the disease. This enhanced expression of BCR-ABL was associated with an increased rate of glycolysis but with a decreased rate of proliferation. The higher level of BCR-ABL expression in the selected cells correlated with a nonhypoxic induction of hypoxia-inducible factor-1alpha (HIF-1alpha) that was required for cells to tolerate enhanced BCR-ABL signaling. HIF-1alpha induction resulted in an enhanced rate of glycolysis but with reduced glucose flux through both the tricarboxylic acid cycle and the oxidative arm of the pentose phosphate pathway (PPP). The reduction in oxidative PPP-mediated ribose synthesis was compensated by the HIF-1alpha-dependent activation of the nonoxidative PPP enzyme, transketolase, in imatinib-resistant CML cells. In both primary cultures of cells from patients exhibiting blast transformation and in vivo xenograft tumors, use of oxythiamine, which can inhibit both the pyruvate dehydrogenase complex and transketolase, resulted in enhanced imatinib sensitivity of tumor cells. Together, these results suggest that oxythiamine can enhance imatinib efficacy in patients who present an accelerated form of the disease.
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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 OpenQuestion graph.