Overexpression of Syk tyrosine kinase in peripheral T-cell lymphomas

A. L. Feldman, D. X. Sun, M. E. Law, A. J. Novak, A. D. Attygalle, 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

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107 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1139-1143
Number of pages5
JournalLeukemia
Volume22
Issue number6
DOIs
StatePublished - Jun 2008

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Feldman, A. L., Sun, D. X., Law, M. E., Novak, A. J., Attygalle, A. D., Thorland, E. C., Fink, S. R., Vrana, J. A., Caron, B. L., Morice, W. G., Remstein, E. D., Grogg, K. L., Kurtin, P. J., Macon, W. R., & Dogan, A. (2008). Overexpression of Syk tyrosine kinase in peripheral T-cell lymphomas. Leukemia, 22(6), 1139-1143. https://doi.org/10.1038/leu.2008.77