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Acute Leukemias

FES kinases are required for oncogenic FLT3 signaling

Leukemia volume 24, pages 721–728 (2010)Cite this article

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Abstract

The closely related non-receptor tyrosine kinases FEline Sarcoma (FES) and FEs Related (FER) are activated by cell surface receptors in hematopoietic cells. Despite the early description of oncogenic viral forms of fes, v-fes, and v-fps, the implication of FES and FER in human pathology is not known. We have recently shown that FES but not FER is necessary for oncogenic KIT receptor signaling. Here, we report that both FES and FER kinases are activated in primary acute myeloid leukemia (AML) blasts and in AML cell lines. FES and FER activation is dependent on FLT3 in cell lines harboring constitutively active FLT3 mutants. Moreover, both FES and FER proteins are critical for FLT3-internal tandem duplication (ITD) signaling and for cell proliferation in relevant AML cell lines. FER is required for cell cycle transitions, whereas FES seems necessary for cell survival. We concluded that FES and FER kinases mediate essential non-redundant functions downstream of FLT3-ITD.

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Acknowledgements

We thank Jean-Rémi Galindo for the help with FACS analysis, Michel Pierres and the Monoclonal Antibody facility group IFR137, the Centre de Ressources Biologiques of the Institut Paoli-Calmettes, Brian Druker for sending the MOLM-14 cell line, and Subburaj Ilangumaran for critical reading of the manuscript. EV was supported by PhD fellowships from INSERM/Région Provence-Alpes-Cote-d'Azur and from l'Association pour la Recherche sur le Cancer, and AC by a PhD fellowship from le Ministère de la Recherche. SL acknowledges a postdoctoral fellowship from la Fondation de France. KH is supported by Association Française pour les Initiatives de Recherche sur le Mastocyte et les Mastocytoses. PD and PDS are INSERM scientists. This work was supported by grants from Institut National du Cancer (INCa) and l'Agence Nationale de la Recherche. Our laboratory is supported by la Ligue Nationale Contre le Cancer (équipe labélisée).

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Authors and Affiliations

  1. INSERM, UMR 891, Centre de Recherche en Cancérologie de Marseille, Laboratoire de Signalisation, Hématopoïèse et Mécanismes de l'Oncogenèse, Marseille, France

    E Voisset, S Lopez, A Chaix, C Georges, K Hanssens, P Dubreuil & P De Sepulveda

  2. Institut Paoli-Calmettes, Centre Régional de Lutte Contre le Cancer, Marseille, France

    E Voisset, S Lopez, A Chaix, C Georges, K Hanssens, T Prébet, P Dubreuil & P De Sepulveda

  3. Université de la Méditerranée, Marseille, France

    E Voisset, S Lopez, A Chaix, C Georges, K Hanssens, T Prébet, P Dubreuil & P De Sepulveda

  4. Laboratoire de Pharmacologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Marseille, France

    T Prébet

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  1. E Voisset
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Correspondence to P De Sepulveda.

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Voisset, E., Lopez, S., Chaix, A. et al. FES kinases are required for oncogenic FLT3 signaling. Leukemia 24, 721–728 (2010). https://doi.org/10.1038/leu.2009.301

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