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  • Molecular Targets For Therapy (MTT)
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Molecular Targets for Therapy (MTT)

Increased expression of fibroblast growth factor receptor 3 in CD34+ BCR-ABL+ cells from patients with chronic myeloid leukemia

Leukemia volume 17, pages 2418–2425 (2003)Cite this article

Abstract

Previously, we showed that expression of myeloma-associated (proto)oncogene fibroblast growth factor receptor 3 (FGFR-3) is increased in white blood cells from patients with chronic myeloid leukemia (CML). The abnormal expression was returned back to the normal levels as soon as these patients reconstituted their hematopoiesis following transplantation of allogeneic peripheral blood stem cells. The aims of this study were: (1) to define population(s) of cells overexpressing FGFR-3, and (2) to determine the expression of FGFR-3 during the clinical course of the disease. We show that the vast majority of FGFR-3 transcripts as well as FGFR-3 protein arise from CD34+ BCR-ABL+ cells. Although increased levels of FGFR-3 were found in majority of late chronic phase patients treated with interferon α or hydroxyurea, the expression of FGFR-3 was always lowered following treatment with BCR-ABL tyrosine kinase inhibitor STI571. Compared to unstimulated cells, high levels of FGFR-3 were also identified in CD34+ cells from granulocyte colony-stimulating factor-mobilized blood stem cell harvests from healthy donors, suggesting a potential growth factor-dependent basis for elevated expression of FGFR-3 in CML. These findings have implications for the involvement of FGFR-3 in malignant hematopoiesis and depict FGFR-3 tyrosine kinase in CD34+ leukemic cells as a possible target for tyrosine kinase inhibitors.

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Acknowledgements

We thank all the volunteers for donating blood and J Zemankova and O Lostakova for help in collecting and processing blood samples. We also thank W Wilcox and P Krejci for critical reading of the manuscript and helpful comments, and M Beranek (Centre of Biostatistics and Analyses, Masaryk University Brno) for statistical analyses. This research was supported in part by the Grant Agency of the Czech Republic (301/03/1122), Ministry of Health (MZ 00065269705), Ministry of Education, Youth, and Sports (MSM 432100001, LN 00A065), and Academy of Sciences of the Czech Republic (AV 0Z5039906).

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Authors and Affiliations

  1. Department of Molecular Embryology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Brno, Czech Republic

    P Dvorak, J Faitova & A Hampl

  2. Department of Internal Medicine – Hematooncology, University Hospital Brno, Czech Republic

    D Dvorakova, M Doubek, J Pacholikova & J Mayer

  3. Mendel University Brno, Czech Republic

    P Dvorak & A Hampl

  4. Center for Cell Therapy and Tissue Repair, Charles University, Prague, Czech Republic

    P Dvorak & A Hampl

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Dvorak, P., Dvorakova, D., Doubek, M. et al. Increased expression of fibroblast growth factor receptor 3 in CD34+ BCR-ABL+ cells from patients with chronic myeloid leukemia. Leukemia 17, 2418–2425 (2003). https://doi.org/10.1038/sj.leu.2403152

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