ArticleLeukemia2004
P-glycoprotein-mediated drug efflux is a resistance mechanism of chronic myelogenous leukemia cells to treatment with imatinib mesylate.
Article in Leukemia, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 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
102 citing papers in PubMed, 306 citations in OpenAlex.
- Population Pharmacokinetic Analysis of the Oral Absorption Process and Explaining Intra-Subject Variability in Plasma Exposures of Imatinib in Healthy Volunteers.European journal of drug metabolism and pharmacokinetics · 2016Trial
- Plasma exposure of imatinib and its correlation with clinical response in the Tyrosine Kinase Inhibitor Optimization and Selectivity Trial.Haematologica · 2012Trial
- Phase 1/2 clinical study of dasatinib in Japanese patients with chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia.International journal of hematology · 2009Trial
- Drug resistance in chronic myeloid leukemia: the involvement of Galectin-1 and Galectin-3.Molecular biology reports · 2026Review
- Design, Synthesis, and Biological Evaluation of Efflux-Resistant Imatinib Derivatives.Journal of medicinal chemistry · 2025Article
- Computationally Driven Discovery of a BCR-ABL1 Kinase Inhibitor with Activity in Multidrug-Resistant Chronic Myeloid Leukemia.Journal of medicinal chemistry · 2024Article
- Transporter-Mediated Cellular Distribution of Tyrosine Kinase Inhibitors as a Potential Resistance Mechanism in Chronic Myeloid Leukemia.Pharmaceutics · 2023Review
- Application of physiologically based pharmacokinetic modeling to understand real-world outcomes in patients receiving imatinib for chronic myeloid leukemia.Pharmacology research & perspectives · 2023Observational
- Therapy Resistance and Disease Progression in CML: Mechanistic Links and Therapeutic Strategies.Current hematologic malignancy reports · 2022Review
- Infigratinib (BGJ 398), a Pan-FGFR Inhibitor, Targets P-Glycoprotein and Increases Chemotherapeutic-Induced Mortality of Multidrug-Resistant Tumor Cells.Biomedicines · 2022Article
- Review
- A microfluidic device enabling drug resistance analysis of leukemia cells via coupled dielectrophoretic detection and impedimetric counting.Scientific reports · 2021Article
- Plasma imatinib levels and ABCB1 polymorphism influences early molecular response and failure-free survival in newly diagnosed chronic phase CML patients.Scientific reports · 2020Article
- Metabolic Plasticity Is an Essential Requirement of Acquired Tyrosine Kinase Inhibitor Resistance in Chronic Myeloid Leukemia.Cancers · 2020Article
- Overexpression of P-glycoprotein and resistance to Imatinib in chronic myeloid leukemia patients.Journal of clinical laboratory analysis · 2020Article
- Imatinib mesylate affects extracellular ATP catabolism and expression of NTPDases in a chronic myeloid leukemia cell line.Purinergic signalling · 2020Article
- Cytotoxic Effects of Some Flavonoids and Imatinib on the K562 Chronic Myeloid Leukemia Cell Line: Data Analysis Using the Combination Index MethodBalkan medical journal · 2019Article
- Modelling ponatinib resistance in tyrosine kinase inhibitor-naïve and dasatinib resistantOncotarget · 2018Article
- Concise Review: Chronic Myeloid Leukemia: Stem Cell Niche and Response to Pharmacologic Treatment.Stem cells translational medicine · 2018Review
- Role of Non Receptor Tyrosine Kinases in Hematological Malignances and its Targeting by Natural Products.Molecular cancer · 2018Review
42 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Imatinib (Glivec), STI571) is an intracellular acting drug that demonstrates high activity against BCR-ABL-positive chronic myelogenous leukemia (CML) or acute lymphoblastic leukemia (ALL). However, many patients, especially with advanced disease, develop drug resistance. Here, we show by a novel high-performance liquid chromatography-based method that intracellular levels of imatinib decrease in P-glycoprotein (Pgp)-positive leukemic cells. In a model of K562 cells with gradually increasing Pgp expression, a Pgp-dependent decline of intracellular imatinib levels was observed. Decreased imatinib levels were associated with a retained phosphorylation pattern of the Bcr-Abl target Crkl and loss of effect of imatinib on cellular proliferation and apoptosis. The modulation of Pgp by cyclosporin A (CSA) readily restored imatinib cytotoxicity in these cells. Finally, we provide first data showing a biological effect of Pgp modulation in the imatinib treatment of a patient with BCR-ABL-positive ALL. MDR1 overexpression must therefore be considered as an important clinical mechanism in the diversity of resistance development to imatinib treatment.
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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.