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Molecular Targets for Therapy

Overexpression of Syk tyrosine kinase in peripheral T-cell lymphomas

Leukemia volume 22, pages 1139–1143 (2008)Cite this article

Abstract

Peripheral T-cell lymphomas (PTCLs) are fatal in the majority of patients and novel treatments, such as protein tyrosine kinase (PTK) inhibition, are needed. The recent finding of SYK/ITK translocations in rare PTCLs led us to examine the expression of Syk PTK in 141 PTCLs. Syk was positive by immunohistochemistry (IHC) in 133 PTCLs (94%), whereas normal T cells were negative. Western blot on frozen tissue (n=6) and flow cytometry on cell suspensions (n=4) correlated with IHC results in paraffin. Additionally, western blot demonstrated that Syk-positive PTCLs show tyrosine (525/526) phosphorylation, known to be required for Syk activation. Fluorescence in situ hybridization showed no SYK/ITK translocation in 86 cases. Overexpression of Syk, phosphorylation of its Y525/526 residues and the availability of orally available Syk inhibitors suggest that Syk merits further evaluation as a candidate target for pharmacologic PTK inhibition in patients with PTCL.

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Acknowledgements

We acknowledge the support from the Iowa/Mayo Lymphoma SPORE grant from the National Cancer Institute (P50 CA97274). In addition, we thank Ms Connie Lesnick for help with flow cytometry, Dr B Streubel for providing control specimens with the SYK/ITK translocation and Ms Monica Kramer and Ms Carrie Stevenson for administrative assistance.

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Authors and Affiliations

  1. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

    A L Feldman, D X Sun, M E Law, E C Thorland, S R Fink, J A Vrana, B L Caron, W G Morice, E D Remstein, K L Grogg, P J Kurtin, W R Macon & A Dogan

  2. Department of Hematology, Mayo Clinic, Rochester, MN, USA

    A J Novak

  3. Department of Histopathology, Royal Marsden Hospital, London, UK

    A D Attygalle

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  1. A L Feldman
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Correspondence to A L Feldman.

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Feldman, A., Sun, D., Law, M. et al. Overexpression of Syk tyrosine kinase in peripheral T-cell lymphomas. Leukemia 22, 1139–1143 (2008). https://doi.org/10.1038/leu.2008.77

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