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Overexpression of Syk tyrosine kinase in peripheral T-cell lymphomas

A L Feldman1, D X Sun, M E Law

  • 1Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA. feldman.andrew@mayo.edu

Leukemia
|April 11, 2008
PubMed

Insights

Peripheral T-cell lymphomas (PTCLs) show high expression of Syk protein tyrosine kinase (PTK). This finding suggests Syk PTK inhibition as a potential novel treatment strategy for PTCL patients.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Peripheral T-cell lymphomas (PTCLs) are aggressive cancers with poor prognoses.
  • Novel therapeutic targets are urgently needed for PTCL treatment.

Purpose of the Study:

  • To investigate the expression and activation status of Syk protein tyrosine kinase (PTK) in PTCLs.
  • To evaluate Syk as a potential therapeutic target in PTCL.

Main Methods:

  • Immunohistochemistry (IHC) was used to assess Syk expression in 141 PTCL samples.
  • Western blot and flow cytometry were employed to confirm Syk expression and activation.
  • Fluorescence in situ hybridization (FISH) was performed to detect SYK/ITK translocations.

Main Results:

  • Syk was expressed in 94% of PTCLs (133/141) but not in normal T cells.
  • Syk-positive PTCLs exhibited tyrosine phosphorylation at residues 525/526, indicating activation.
  • No SYK/ITK translocations were found in 86 analyzed cases.

Conclusions:

  • Syk PTK is frequently overexpressed and activated in PTCLs.
  • The absence of SYK/ITK translocations suggests alternative mechanisms for Syk activation in PTCL.
  • Syk is a promising candidate target for pharmacologic inhibition in PTCL treatment.

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