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Activity of fibroblast growth factor receptor inhibitors TKI258, ponatinib and AZD4547 against TPR‑FGFR1 fusion

  • Authors:
    • Xu‑Hua Qiu
    • Feng Li
    • Hong‑Qin Cao
    • Jing‑Jing Shao
    • Jian‑Gang Mei
    • Han‑Qing Li
    • Yong‑Ping Zhai
  • View Affiliations / Copyright

    Affiliations: Department of Hematology, Jinling Hospital, Nanjing, Jiangsu 210002, P.R. China
    Copyright: © Qiu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1024-1030
    |
    Published online on: January 24, 2017
       https://doi.org/10.3892/mmr.2017.6140
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Abstract

8p11 myeloproliferative syndrome (EMS) is a rare disease characterized by the constitutive activation of fibroblast growth factor receptor 1 (FGFR1). To date, four cases of EMS with the chromosomal translocation, t(1;8)(q25;p11.2), have been reported. In the present study, TPR‑FGFR1‑expressing Baf3 cells were established and confirmed by polymerase chain reaction. To identify the most promising drug for EMS, the activities and associated mechanism of three tyrosine kinase inhibitors (TKIs), TKI258, ponatinib and AZD4547, against TPR‑FGFR1 were tested by MTT assay, flow cytometry and western blot. The data demonstrated that TPR‑FGFR1 was localized in the cytoplasm, and was able to transform interleukin-3-dependent hematopoietic Baf3 cells into growth factor‑independent cells. All of the three TKIs markedly inhibited the proliferation of TPR‑FGFR1‑expressing Baf3 cells, and the activation of FGFR1 and the downstream signaling molecules, extracellular signal‑regulated kinase 1/2, phospholipiase Cγ and signal transducer and activator of transcription 5. AZD4547 was the most efficient drug, and TKI258 was the least. By contrast, no significant difference was found among the three drugs on their effect on cell apoptosis. Taken together, the data obtained in the present study suggested that AZD4547 had increased potency, compared with TKI258 and ponatinib, for the treatment of EMS.
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Copy and paste a formatted citation
Spandidos Publications style
Qiu XH, Li F, Cao HQ, Shao JJ, Mei JG, Li HQ and Zhai YP: Activity of fibroblast growth factor receptor inhibitors TKI258, ponatinib and AZD4547 against TPR‑FGFR1 fusion. Mol Med Rep 15: 1024-1030, 2017.
APA
Qiu, X., Li, F., Cao, H., Shao, J., Mei, J., Li, H., & Zhai, Y. (2017). Activity of fibroblast growth factor receptor inhibitors TKI258, ponatinib and AZD4547 against TPR‑FGFR1 fusion. Molecular Medicine Reports, 15, 1024-1030. https://doi.org/10.3892/mmr.2017.6140
MLA
Qiu, X., Li, F., Cao, H., Shao, J., Mei, J., Li, H., Zhai, Y."Activity of fibroblast growth factor receptor inhibitors TKI258, ponatinib and AZD4547 against TPR‑FGFR1 fusion". Molecular Medicine Reports 15.3 (2017): 1024-1030.
Chicago
Qiu, X., Li, F., Cao, H., Shao, J., Mei, J., Li, H., Zhai, Y."Activity of fibroblast growth factor receptor inhibitors TKI258, ponatinib and AZD4547 against TPR‑FGFR1 fusion". Molecular Medicine Reports 15, no. 3 (2017): 1024-1030. https://doi.org/10.3892/mmr.2017.6140
Copy and paste a formatted citation
x
Spandidos Publications style
Qiu XH, Li F, Cao HQ, Shao JJ, Mei JG, Li HQ and Zhai YP: Activity of fibroblast growth factor receptor inhibitors TKI258, ponatinib and AZD4547 against TPR‑FGFR1 fusion. Mol Med Rep 15: 1024-1030, 2017.
APA
Qiu, X., Li, F., Cao, H., Shao, J., Mei, J., Li, H., & Zhai, Y. (2017). Activity of fibroblast growth factor receptor inhibitors TKI258, ponatinib and AZD4547 against TPR‑FGFR1 fusion. Molecular Medicine Reports, 15, 1024-1030. https://doi.org/10.3892/mmr.2017.6140
MLA
Qiu, X., Li, F., Cao, H., Shao, J., Mei, J., Li, H., Zhai, Y."Activity of fibroblast growth factor receptor inhibitors TKI258, ponatinib and AZD4547 against TPR‑FGFR1 fusion". Molecular Medicine Reports 15.3 (2017): 1024-1030.
Chicago
Qiu, X., Li, F., Cao, H., Shao, J., Mei, J., Li, H., Zhai, Y."Activity of fibroblast growth factor receptor inhibitors TKI258, ponatinib and AZD4547 against TPR‑FGFR1 fusion". Molecular Medicine Reports 15, no. 3 (2017): 1024-1030. https://doi.org/10.3892/mmr.2017.6140
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