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Chronic Myeloproliferative Neoplasias

Centrosomal targeting of tyrosine kinase activity does not enhance oncogenicity in chronic myeloproliferative disorders

Leukemia volume 26, pages 728–735 (2012)Cite this article

Abstract

Constitutive tyrosine kinase activation by reciprocal chromosomal translocation is a common pathogenetic mechanism in chronic myeloproliferative disorders. Since centrosomal proteins have been recurrently identified as translocation partners of tyrosine kinases FGFR1, JAK2, PDGFRα and PDGFRβ in these diseases, a role for the centrosome in oncogenic transformation has been hypothesized. In this study, we addressed the functional role of centrosomally targeted tyrosine kinase activity. First, centrosomal localization was not routinely found for all chimeric fusion proteins tested. Second, targeting of tyrosine kinases to the centrosome by creating artificial chimeric fusion kinases with the centrosomal targeting domain of AKAP450 failed to enhance the oncogenic transforming potential in both Ba/F3 and U2OS cells, although phospho-tyrosine-mediated signal transduction pathways were initiated at the centrosome. We conclude that the centrosomal localization of constitutively activated tyrosine kinases does not contribute to disease pathogenesis in chronic myeloproliferative disorders.

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Acknowledgements

We thank D Gilliland and E Stover for gently providing Tel-PDGFRβ and FIP1L1-PDGFRα plasmids, A Reiter for the CDK5RAP2-PDGFRα plasmid and M Bornens and Y Hong for ninein plasmids. The pBI-3 vector was kindly provided by H Bujard. We are grateful to the Deutsche José Carreras Leukämie-Stiftung for financial support (DJCLS R 06/04).

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Authors and Affiliations

  1. German Cancer Research Center (DKFZ) and Department of Internal Medicine V, Clinical Cooperation Unit Molecular Hematology/Oncology, University of Heidelberg, Heidelberg, Germany

    T Bochtler, M Kirsch, B Maier, S Anderhub & A Krämer

  2. Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany

    T Bochtler, M Kirsch, A D Ho & A Krämer

  3. Division Systems Biology of Signal Transduction, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, Germany

    J Bachmann & U Klingmüller

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Bochtler, T., Kirsch, M., Maier, B. et al. Centrosomal targeting of tyrosine kinase activity does not enhance oncogenicity in chronic myeloproliferative disorders. Leukemia 26, 728–735 (2012). https://doi.org/10.1038/leu.2011.283

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