Overexpression of Syk tyrosine kinase in peripheral T-cell lymphomas

Autor: Bolette L. Caron, Ellen D. Remstein, Erik C. Thorland, Mark E. Law, William R. Macon, Ahmet Dogan, David X. Sun, Andrew L. Feldman, Ayoma D. Attygalle, Paul J. Kurtin, Stephanie R. Fink, Karen L. Grogg, William G. Morice, Anne J. Novak, Julie A. Vrana
Jazyk: angličtina
Rok vydání: 2008
Předmět:
Adult
Male
Cancer Research
Adolescent
T cell
Blotting
Western

Syk
Biology
environment and public health
Article
Translocation
Genetic

Immunophenotyping
Immunoenzyme Techniques
Western blot
hemic and lymphatic diseases
medicine
Humans
Syk Kinase
Tyrosine
Phosphorylation
Child
In Situ Hybridization
Fluorescence

Aged
Aged
80 and over

medicine.diagnostic_test
Intracellular Signaling Peptides and Proteins
Lymphoma
T-Cell
Peripheral

hemic and immune systems
Hematology
Middle Aged
Protein-Tyrosine Kinases
Flow Cytometry
Lymphoma
T-Cell
Cutaneous

Blot
Lymphoma
Extranodal NK-T-Cell

enzymes and coenzymes (carbohydrates)
medicine.anatomical_structure
Oncology
Child
Preschool

Cancer research
Immunohistochemistry
Chromosomes
Human
Pair 5

Lymphoma
Large-Cell
Anaplastic

Female
biological phenomena
cell phenomena
and immunity

Chromosomes
Human
Pair 9

Tyrosine kinase
Popis: 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.
Databáze: OpenAIRE