Trial reportExperimental hematology2014
Identification of Ponatinib as a potent inhibitor of growth, migration, and activation of neoplastic eosinophils carrying FIP1L1-PDGFRA.
Trial report in Experimental hematology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 43 citations in OpenAlex.
- Symmetric cancer spheroid-fibroblast organization revealed in 3D by high-throughput microscopy.Communications biology · 2026Article
- Synthesis of Novel Acetylene-Containing Phosphonates, Their Antiviral Activity, and Their Cytotoxicity to Different Cancer Cell Lines.Molecules (Basel, Switzerland) · 2026Article
- The Adverse Impact of Tyrosine Kinase Inhibitors on Wound Healing and Repair.International wound journal · 2025Review
- CLIP-170S is a microtubule +TIP variant that confers resistance to taxanes by impairing drug-target engagement.Developmental cell · 2021Article
- Myeloid Neoplasm with PDGFRA Rearrangement Manifesting as a Retromolar Pad Mass.Head and neck pathology · 2021Article
- Zebrafish as a Model for In-Depth Mechanistic Study for Stroke.Translational stroke research · 2021Review
- Eosinophils and eosinophil-associated disorders: immunological, clinical, and molecular complexity.Seminars in immunopathology · 2021Review
- Cardiotoxicity of the BCR-ABL1 tyrosine kinase inhibitors: Emphasis on ponatinib.International journal of cardiology · 2020Review
- S100A8 and S100A9 Promote Apoptosis of Chronic Eosinophilic Leukemia Cells.Frontiers in immunology · 2020Article
- Review
- Ponatinib exerts anti-angiogenic effects in the zebrafish and human umbilical vein endothelial cells via blocking VEGFR signaling pathway.Oncotarget · 2018Article
- The JAK2/STAT5 signaling pathway as a potential therapeutic target in canine mastocytoma.Veterinary and comparative oncology · 2018Article
- Gastrointestinal stromal tumors (GISTs): point mutations matter in management, a review.Journal of gastrointestinal oncology · 2017Review
- The novel kinase inhibitor ponatinib is an effective anti-angiogenic agent against neuroblastoma.Investigational new drugs · 2016Article
- Pharmacological targeting of the PDGF-CC signaling pathway for blood-brain barrier restoration in neurological disorders.Pharmacology & therapeutics · 2016Review
- Platelet-derived growth factor receptor/platelet-derived growth factor (PDGFR/PDGF) system is a prognostic and treatment response biomarker with multifarious therapeutic targets in cancers.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- Hypereosinophilic Syndrome.Clinical reviews in allergy & immunology · 2016Review
- Kinase Inhibitor Profiling Reveals Unexpected Opportunities to Inhibit Disease-Associated Mutant Kinases.Cell reports · 2016Article
- How I treat hypereosinophilic syndromes.Blood · 2015Review
- The BCR-ABL inhibitor ponatinib inhibits platelet immunoreceptor tyrosine-based activation motif (ITAM) signaling, platelet activation and aggregate formation under shear.Thrombosis research · 2015Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
In chronic eosinophilic leukemia, the transforming oncoprotein FIP1L1-PDGFRA is a major target of therapy. In most patients, the tyrosine kinase inhibitor (TKI) imatinib induces complete remission. For patients who are intolerant or resistant, novel TKIs have been proposed. We examined the in vitro effects of 14 kinase blockers on growth and function of EOL-1 cells, a FIP1L1-PDGFRA(+) eosinophil cell line. Major growth-inhibitory effects were seen with all PDGFR-blocking agents, with IC50 values in the low nanomolar range: ponatinib, 0.1-0.2 nmol/L; sorafenib, 0.1-0.2 nmol/L; masitinib, 0.2-0.5 nmol/L; nilotinib, 0.2-1.0 nmol/L; dasatinib, 0.5-2.0 nmol/L; sunitinib, 1-2 nmol/L; midostaurin, 5-10 nmol/L. These drugs were also found to block activation of PDGFR-downstream signaling molecules, including Akt, S6, and STAT5 in EOL-1 cells. All effective TKIs produced apoptosis in EOL-1 cells as determined by microscopy, Annexin-V/PI, and caspase-3 staining. In addition, PDGFR-targeting TKIs were found to inhibit cytokine-induced migration of EOL-1 cells. In all bioassays used, ponatinib was found to be the most potent compound in EOL-1 cells. In addition, ponatinib was found to downregulate expression of the activation-linked surface antigen CD63 on EOL-1 cells and to suppress the growth of primary neoplastic eosinophils. We also examined drug effects on Ba/F3 cells expressing two clinically relevant, imatinib-resistant, mutant forms of FIP1L1-PDGFRA, namely T674I and D842V. Strong inhibitory effects on both mutants were seen only with ponatinib. In summary, novel PDGFR-targeting TKIs may be alternative agents for the treatment of patients with imatinib-resistant chronic eosinophilic leukemia. Although several different PDGFR-targeting agents are effective, the most potent drug appears to be ponatinib.
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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.