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
- 1Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
- 2Department of Hematology, Mayo Clinic, Rochester, MN, USA
- 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.
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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