ArticleLeukemia2011
The MEK inhibitor PD184352 enhances BMS-214662-induced apoptosis in CD34+ CML stem/progenitor cells.
Article in Leukemia, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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.
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Who cites it
25 citing papers in PubMed, 48 citations in OpenAlex.
- Autophagy and Cancer: Insights into Molecular Mechanisms and Therapeutic Approaches for Chronic Myeloid Leukemia.Biomolecules · 2025Review
- Effects of a Functional Ice Cream Enriched with Milk Proteins on Bone Metabolism: A Feasibility Clinical Study and In Vitro Investigation.Nutrients · 2023Article
- Therapy Resistance and Disease Progression in CML: Mechanistic Links and Therapeutic Strategies.Current hematologic malignancy reports · 2022Review
- A superior loading control for the cellular thermal shift assay.Scientific reports · 2022Article
- The high-risk HPV E6 proteins modify the activity of the eIF4E protein via the MEK/ERK and AKT/PKB pathways.FEBS open bio · 2020Article
- DYRK2 controls a key regulatory network in chronic myeloid leukemia stem cells.Experimental & molecular medicine · 2020Review
- Druggable Biochemical Pathways and Potential Therapeutic Alternatives to Target Leukemic Stem Cells and Eliminate the Residual Disease in Chronic Myeloid Leukemia.International journal of molecular sciences · 2019Review
- Inhibition of GSK3 and MEK induced cancer stem cell generation via the Wnt and MEK signaling pathways.Oncology reports · 2018Article
- Article
- Predicting Drug Combination Index and Simulating the Network-Regulation Dynamics by Mathematical Modeling of Drug-Targeted EGFR-ERK Signaling Pathway.Scientific reports · 2017Article
- Characteristics and mutation analysis of Ph-positive leukemia patients with T315I mutation receiving tyrosine kinase inhibitors.OncoTargets and therapy · 2017Article
- Article
- Identification of Bisindolylmaleimide IX as a potential agent to treat drug-resistant BCR-ABL positive leukemia.Oncotarget · 2016Article
- Article
- Potential role of Notch signalling in CD34+ chronic myeloid leukaemia cells: cross-talk between Notch and BCR-ABL.PloS one · 2015Article
- Antitumor activity of S116836, a novel tyrosine kinase inhibitor, against imatinib-resistant FIP1L1-PDGFRα-expressing cells.Oncotarget · 2014Article
- Wogonin induces cell cycle arrest and erythroid differentiation in imatinib-resistant K562 cells and primary CML cells.Oncotarget · 2014Article
- A therapeutically targetable mechanism of BCR-ABL-independent imatinib resistance in chronic myeloid leukemia.Science translational medicine · 2014Article
- The antiproliferative activity of kinase inhibitors in chronic myeloid leukemia cells is mediated by FOXO transcription factors.Stem cells (Dayton, Ohio) · 2014Article
- Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
The cytotoxic farnesyl transferase inhibitor BMS-214662 has been shown to potently induce mitochondrial apoptosis in primitive CD34+ chronic myeloid leukaemia (CML) stem/progenitor cells. Here, to enhance the BMS-214662 apoptotic effect, we further targeted the extracellular signal-regulated kinase (ERK) pathway, downstream of BCR-ABL, by treating CD34+ CML stem/progenitor cells with a highly selective adenosine triphosphate (ATP) non-competitive MEK inhibitor, PD184352. PD184352 increased the apoptotic effect of BMS-214662 in a CML blast crisis cell line, K562, and in primary chronic phase CD34+ CML cells. Compared with BMS-214662, after combination treatment we observed inhibition of ERK phosphorylation, increased Annexin-V levels, caspase-3, -8 and -9 activation and potentiated mitochondrial damage, associated with decreased levels of anti-apoptotic BCL-2 family protein MCL-1. Inhibition of K-RAS function by a dominant-negative mutant resulted in CML cell death and this process was further enhanced by the addition of BMS-214662 and PD184352. Together, these findings suggest that the addition of a MEK inhibitor improves the ability of BMS-214662 to selectively target CML stem/progenitor cells, notoriously insensitive to tyrosine kinase inhibitor treatment and presumed to be responsible for the persistence and relapse 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.