ArticleBlood2017
Targeting chronic myeloid leukemia stem cells with the hypoxia-inducible factor inhibitor acriflavine.
Article in Blood, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
What it found
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Who cites it
47 citing papers in PubMed, 80 citations in OpenAlex.
- Feedback regulation between histone H3 lysine 18 lactylation and TROP2-mediated glycolysis drives metastatic progression of colorectal cancer.Clinical and translational medicine · 2026Article
- Lactate-mediated activation of GPR81 regulates BCR/Abl protein expression in chronic myeloid leukemia cells selected under low oxygen tension.The Journal of pathology · 2025Article
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- Rationally designed BCR-ABL kinase inhibitors for improved leukemia treatment via covalent and pro-/dual-drug targeting strategies.Journal of advanced research · 2025Article
- BCR::ABL1 expression in chronic myeloid leukemia cells in low oxygen is regulated by glutamine via CD36-mediated fatty acid uptake.Cancer cell international · 2025Article
- BCR::ABL1-induced mitochondrial morphological alterations as a potential clinical biomarker in chronic myeloid leukemia.Cancer science · 2025Article
- Hypoxia-inducible transcription factors: architects of tumorigenesis and targets for anticancer drug discovery.Transcription · 2025Review
- Chiglitazar diminishes the warburg effect through PPARγ/mTOR/PKM2 and increases the sensitivity of imatinib in chronic myeloid leukemia.Experimental hematology & oncology · 2024Article
- Novel targeted therapies in chronic myeloid leukemia.Pharmaceutical science advances · 2024Review
- Cell-Membrane-Coated Metal-Organic Framework Nanocarrier Combining Chemodynamic Therapy for the Inhibition of Hepatocellular Carcinoma Proliferation.Pharmaceutics · 2024Article
- HIF-1α is an important regulator of IL-8 expression in human bone marrow stromal cells under hypoxic microenvironment.Protoplasma · 2024Article
- Article
- Article
- mTORC2 Is Activated under Hypoxia and Could Support Chronic Myeloid Leukemia Stem Cells.International journal of molecular sciences · 2023Article
- Hypoxia-associated genes predicting future risk of myocardial infarction: a GEO database-based study.Frontiers in cardiovascular medicine · 2023Article
- Ex Vivo Expansion of Phenotypic and Transcriptomic Chronic Myeloid Leukemia Stem Cells.Experimental hematology · 2022Article
- Acriflavine, an Acridine Derivative for Biomedical Application: Current State of the Art.Journal of medicinal chemistry · 2022Review
- Targeting HIF-1α by Natural and Synthetic Compounds: A Promising Approach for Anti-Cancer Therapeutics Development.Molecules (Basel, Switzerland) · 2022Review
- Adaptation to Hypoxia May Promote Therapeutic Resistance to Androgen Receptor Inhibition in Triple-Negative Breast Cancer.International journal of molecular sciences · 2022Review
- Lactate Maintains BCR/Abl Expression and Signaling in Chronic Myeloid Leukemia Cells Under Nutrient Restriction.Oncology research · 2022Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
Chronic myeloid leukemia (CML) is a hematopoietic stem cell (HSC)-driven neoplasia characterized by expression of the constitutively active tyrosine kinase BCR/Abl. CML therapy based on tyrosine kinase inhibitors (TKIs) is highly effective in inducing remission but not in targeting leukemia stem cells (LSCs), which sustain minimal residual disease and are responsible for CML relapse following discontinuation of treatment. The identification of molecules capable of targeting LSCs appears therefore of primary importance to aim at CML eradication. LSCs home in bone marrow areas at low oxygen tension, where HSCs are physiologically hosted. This study addresses the effects of pharmacological inhibition of hypoxia-inducible factor-1 (HIF-1), a critical regulator of LSC survival, on the maintenance of CML stem cell potential. We found that the HIF-1 inhibitor acriflavine (ACF) decreased survival and growth of CML cells. These effects were paralleled by decreased expression of c-Myc and stemness-related genes. Using different in vitro stem cell assays, we showed that ACF, but not TKIs, targets the stem cell potential of CML cells, including primary cells explanted from 12 CML patients. Moreover, in a murine CML model, ACF decreased leukemia development and reduced LSC maintenance. Importantly, ACF exhibited significantly less-severe effects on non-CML hematopoietic cells in vitro and in vivo. Thus, we propose ACF, a US Food and Drug Administration (FDA)-approved drug for nononcological use in humans, as a novel therapeutic approach to prevent CML relapse and, in combination with TKIs, enhance induction of remission.
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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.