Original Article

Leukemia (2008) 22, 1139–1143; doi:10.1038/leu.2008.77; published online 10 April 2008

Molecular Targets for Therapy

Overexpression of Syk tyrosine kinase in peripheral T-cell lymphomas

A L Feldman1, D X Sun1, M E Law1, A J Novak2, A D Attygalle3, E C Thorland1, S R Fink1, J A Vrana1, B L Caron1, W G Morice1, E D Remstein1, K L Grogg1, P J Kurtin1, W R Macon1 and A Dogan1

  1. 1Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
  2. 2Department of Hematology, Mayo Clinic, Rochester, MN, USA
  3. 3Department of Histopathology, Royal Marsden Hospital, London, UK

Correspondence: Dr AL Feldman, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA. E-mail: feldman.andrew@mayo.edu

Received 3 January 2008; Revised 11 February 2008; Accepted 29 February 2008; Published online 10 April 2008.

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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.

Keywords:

peripheral T-cell lymphoma, Syk, tyrosine kinase, phosphorylation

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