ArticleBlood2014
Ponatinib overcomes FGF2-mediated resistance in CML patients without kinase domain mutations.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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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
34 citing papers in PubMed, 49 citations in OpenAlex.
- Blockade of FGF2/FGFR2 partially overcomes bone marrow mesenchymal stromal cells mediated progression of T-cell acute lymphoblastic leukaemia.Cell death & disease · 2022Article
- Understanding Drug Sensitivity and Tackling Resistance in Cancer.Cancer research · 2022Article
- BCOR and BCORL1 Mutations Drive Epigenetic Reprogramming and Oncogenic Signaling by Unlinking PRC1.1 from Target Genes.Blood cancer discovery · 2022Article
- Chronic myeloid leukemia stem cells: targeting therapeutic implications.Stem cell research & therapy · 2021Review
- Shedding Light on Targeting Chronic Myeloid Leukemia Stem Cells.Journal of clinical medicine · 2021Review
- The AML microenvironment catalyzes a stepwise evolution to gilteritinib resistance.Cancer cell · 2021Article
- Mesenchymal soluble factors confer imatinib drug resistance in chronic myelogenous leukemia cells.Archives of medical science : AMS · 2021Article
- Response and Resistance to BCR-ABL1-Targeted Therapies.Cancer cell · 2020Review
- Loss of FGFR3 Delays Acute Myeloid Leukemogenesis by Programming Weakly Pathogenic CD117-Positive Leukemia Stem-Like Cells.Frontiers in pharmacology · 2020Article
- Bone marrow microenvironment: The guardian of leukemia stem cells.World journal of stem cells · 2019Review
- Chronic myeloid leukemia stem cells.Leukemia · 2019Review
- The RTK Interactome: Overview and Perspective on RTK Heterointeractions.Chemical reviews · 2019Review
- FGF2-FGFR1 signaling regulates release of Leukemia-Protective exosomes from bone marrow stromal cells.eLife · 2019Article
- Review
- K562 chronic myeloid leukemia cells modify osteogenic differentiation and gene expression of bone marrow stromal cells.Journal of cell communication and signaling · 2018Article
- Targeting BCR-ABL-Independent TKI Resistance in Chronic Myeloid Leukemia by mTOR and Autophagy Inhibition.Journal of the National Cancer Institute · 2018Article
- Targeting tumour microenvironment by tyrosine kinase inhibitor.Molecular cancer · 2018Review
- Mesenchymal stem cells show functional defect and decreased anti-cancer effect after exposure to chemotherapeutic drugs.Journal of biomedical science · 2018Article
- Adhesion to stromal cells mediates imatinib resistance in chronic myeloid leukemia through ERK and BMP signaling pathways.Scientific reports · 2017Article
- Targeting the PIM protein kinases for the treatment of a T-cell acute lymphoblastic leukemia subset.Oncotarget · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Development of resistance to kinase inhibitors remains a clinical challenge. Kinase domain mutations are a common mechanism of resistance in chronic myeloid leukemia (CML), yet the mechanism of resistance in the absence of mutations remains unclear. We tested proteins from the bone marrow microenvironment and found that FGF2 promotes resistance to imatinib in vitro. Fibroblast growth factor 2 (FGF2) was uniquely capable of promoting growth in both short- and long-term assays through the FGF receptor 3/RAS/c-RAF/mitogen-activated protein kinase pathway. Resistance could be overcome with ponatinib, a multikinase inhibitor that targets BCR-ABL and FGF receptor. Clinically, we identified CML patients without kinase domain mutations who were resistant to multiple ABL kinase inhibitors and responded to ponatinib treatment. In comparison to CML patients with kinase domain mutations, these patients had increased FGF2 in their bone marrow when analyzed by immunohistochemistry. Moreover, FGF2 in the marrow decreased concurrently with response to ponatinib, further suggesting that FGF2-mediated resistance is interrupted by FGF receptor inhibition. These results illustrate the clinical importance of ligand-induced resistance to kinase inhibitors and support an approach of developing rational inhibitor combinations to circumvent resistance.
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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.