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Characterization of the chronic myelomonocytic leukemia associated TEL-PDGFβR fusion protein

Oncogene volume 18, pages 7055–7062 (1999)Cite this article

Abstract

The t(5;12) translocation, associated with chronic myelomonocytic leukemia, generates a novel gene encoding a protein, TEL-PDGFβR, composed of the 154 amino-terminal amino acids of the transcription factor TEL and the transmembrane and intracellular part of the PDGF β-receptor (PDGFβR). TEL also occurs as a tumor-associated fusion partner for the tyrosine kinases c-ABL, JAK2 and TRK-C. Previous studies have demonstrated growth promoting activity of TEL-PDGFβR and also indicated that the TEL moiety activates the tyrosine kinase of the PDGFβR through the formation of TEL-PDGFβR oligomers. We demonstrate that tyrosine phosphorylation of the fusion protein can be attenuated through overexpression of the TEL part of TEL-PDGFβR, suggesting a strategy for antagonizing the signaling of TEL-PDGFβR, and other TEL-fusion proteins containing tyrosine kinase domains. Comparison of BaF/3 cell lines expressing TEL-PDGFβR and ligand-stimulated PDGFβR revealed that only TEL-PDGFβR expression conferred IL-3-independent growth, suggesting differences in signaling capacity of the two proteins. Finally, tyrosine residues 17 and 27 in TEL-PDGFβR was identified as autophosphorylation sites in TEL-PDGFβR.

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Acknowledgements

We thank Christer Wernstedt for radio-sequencing of peptides, Dr Alexander Levitzki for providing us with the PDGF receptor kinase inhibitor AG1296, Gudrun Bäckström for valuable contributions to this project and Ingegärd Schiller for expert secretarial assistance.

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Author notes

  1. T Sjöblom and A Boureux contributed equally to this paper

Authors and Affiliations

  1. Ludwig Institute for Cancer Research, Box 595, Uppsala, S-751 24, Sweden

    Tobias Sjöblom, Lars Rönnstrand, Carl-Henrik Heldin & Arne Östman

  2. CNRS UMR 146, Institut Curie-Section de Rechèrche, Centre Universitaire, Orsay, 91405, France

    Anthony Boureux & Jacques Ghysdael

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  1. Tobias Sjöblom
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  2. Anthony Boureux
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Sjöblom, T., Boureux, A., Rönnstrand, L. et al. Characterization of the chronic myelomonocytic leukemia associated TEL-PDGFβR fusion protein. Oncogene 18, 7055–7062 (1999). https://doi.org/10.1038/sj.onc.1203190

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