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
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Adult
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Aged
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Aged, 80 and over
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Blotting, Western
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Child
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Child, Preschool
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Chromosomes, Human, Pair 5 / genetics
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Chromosomes, Human, Pair 9 / genetics
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Female
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Flow Cytometry
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Humans
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Immunoenzyme Techniques
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Immunophenotyping
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In Situ Hybridization, Fluorescence
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism*
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Lymphoma, Extranodal NK-T-Cell / enzymology
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Lymphoma, Extranodal NK-T-Cell / genetics
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Lymphoma, Extranodal NK-T-Cell / pathology
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Lymphoma, Large-Cell, Anaplastic / enzymology
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Lymphoma, Large-Cell, Anaplastic / genetics
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Lymphoma, Large-Cell, Anaplastic / pathology
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Lymphoma, T-Cell, Cutaneous / enzymology
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Lymphoma, T-Cell, Cutaneous / genetics
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Lymphoma, T-Cell, Cutaneous / pathology
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Lymphoma, T-Cell, Peripheral / enzymology*
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Lymphoma, T-Cell, Peripheral / genetics
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Lymphoma, T-Cell, Peripheral / pathology
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Male
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Middle Aged
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Phosphorylation
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / metabolism*
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Syk Kinase
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Translocation, Genetic
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Tyrosine / metabolism
Substances
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Intracellular Signaling Peptides and Proteins
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Tyrosine
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Protein-Tyrosine Kinases
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SYK protein, human
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Syk Kinase
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emt protein-tyrosine kinase