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Acute Leukemias

Activation of FGFR1β signaling pathway promotes survival, migration and resistance to chemotherapy in acute myeloid leukemia cells

Leukemia volume 20, pages 979–986 (2006)Cite this article

Abstract

Fibroblast growth factors (FGFs) are important regulators of hematopoiesis and have been implicated in the tumorigenesis of solid tumors. Recent evidence suggests that FGF signaling through FGF receptors (FGFRs) may play a role in the proliferation of subsets of acute myeloid leukemias (AMLs). However, the precise mechanism and specific FGF receptors that support leukemic cell growth are not known. We show that FGF-2, through activation of FGFR1β signaling, promotes survival, proliferation and migration of AML cells. Stimulation of FGFR1β results in phosphoinositide 3-kinase (PI3-K)/Akt activation and inhibits chemotherapy-induced apoptosis of leukemic cells. Neutralizing FGFR1-specific antibody abrogates the physiologic and chemoprotective effects of FGF-2/FGFR1β signaling and inhibits tumor growth in mice xenotransplanted with human AML. These data suggest that activation of FGF-2/FGFR1β supports progression and chemoresistance in subsets of AML. Therefore, FGFR1 targeting may be of therapeutic benefit in subsets of AML.

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Acknowledgements

MAK is supported in part by grants from the Children's Cancer Research Fund and the Hope Street Kids Cancer Foundation.

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Authors and Affiliations

  1. Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    M A Karajannis

  2. Weill Medical College of Cornell University, New York, NY, USA

    M A Karajannis, L Vincent, S V Shmelkov, F Zhang, E J Feldman & S Rafii

  3. ImClone Systems Inc., New York, NY, USA

    R DiRenzo, P Bohlen, Z Zhu, H Sun & P Kussie

Authors
  1. M A Karajannis
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  2. L Vincent
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  4. S V Shmelkov
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  6. E J Feldman
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  7. P Bohlen
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  11. S Rafii
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Correspondence to S Rafii.

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Karajannis, M., Vincent, L., DiRenzo, R. et al. Activation of FGFR1β signaling pathway promotes survival, migration and resistance to chemotherapy in acute myeloid leukemia cells. Leukemia 20, 979–986 (2006). https://doi.org/10.1038/sj.leu.2404203

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