Overexpression of Syk tyrosine kinase in peripheral T-cell lymphomas

Leukemia. 2008 Jun;22(6):1139-43. doi: 10.1038/leu.2008.77. Epub 2008 Apr 10.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Blotting, Western
  • Child
  • Child, Preschool
  • Chromosomes, Human, Pair 5 / genetics
  • Chromosomes, Human, Pair 9 / genetics
  • Female
  • Flow Cytometry
  • Humans
  • Immunoenzyme Techniques
  • Immunophenotyping
  • In Situ Hybridization, Fluorescence
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Lymphoma, Extranodal NK-T-Cell / enzymology
  • Lymphoma, Extranodal NK-T-Cell / genetics
  • Lymphoma, Extranodal NK-T-Cell / pathology
  • Lymphoma, Large-Cell, Anaplastic / enzymology
  • Lymphoma, Large-Cell, Anaplastic / genetics
  • Lymphoma, Large-Cell, Anaplastic / pathology
  • Lymphoma, T-Cell, Cutaneous / enzymology
  • Lymphoma, T-Cell, Cutaneous / genetics
  • Lymphoma, T-Cell, Cutaneous / pathology
  • Lymphoma, T-Cell, Peripheral / enzymology*
  • Lymphoma, T-Cell, Peripheral / genetics
  • Lymphoma, T-Cell, Peripheral / pathology
  • Male
  • Middle Aged
  • Phosphorylation
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • Syk Kinase
  • Translocation, Genetic
  • Tyrosine / metabolism

Substances

  • Intracellular Signaling Peptides and Proteins
  • Tyrosine
  • Protein-Tyrosine Kinases
  • SYK protein, human
  • Syk Kinase
  • emt protein-tyrosine kinase