Overexpression of Syk tyrosine kinase in peripheral T-cell lymphomas

A. L. Feldman; D. X. Sun; M. E. Law; A. J. Novak; A. D. Attygalle; E. C. Thorland; S. R. Fink; J. A. Vrana; B. L. Caron; W. G. Morice; E. D. Remstein; K. L. Grogg; P. J. Kurtin; W. R. Macon; A. Dogan

doi:10.1038/leu.2008.77

Overexpression of Syk tyrosine kinase in peripheral T-cell lymphomas

A. L. Feldman, D. X. Sun, M. E. Law, A. J. Novak, A. D. Attygalle, E. C. Thorland, S. R. Fink, J. A. Vrana, B. L. Caron, W. G. Morice, E. D. Remstein, K. L. Grogg, P. J. Kurtin, W. R. Macon, A. Dogan

Research output: Contribution to journal › Article › peer-review

112 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1139-1143
Number of pages	5
Journal	Leukemia
Volume	22
Issue number	6
DOIs	https://doi.org/10.1038/leu.2008.77
State	Published - Jun 2008

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

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@article{a7b3b8cbdd264394bb4e30062eea82d3,

title = "Overexpression of Syk tyrosine kinase in peripheral T-cell lymphomas",

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.",

author = "Feldman, {A. L.} and Sun, {D. X.} and Law, {M. E.} and Novak, {A. J.} and Attygalle, {A. D.} and Thorland, {E. C.} and Fink, {S. R.} and Vrana, {J. A.} and Caron, {B. L.} and Morice, {W. G.} and Remstein, {E. D.} and Grogg, {K. L.} and Kurtin, {P. J.} and Macon, {W. R.} and A. Dogan",

note = "Funding Information: We acknowledge the support from the Iowa/Mayo Lymphoma SPORE grant from the National Cancer Institute (P50 CA97274). In addition, we thank Ms Connie Lesnick for help with flow cytometry, Dr B Streubel for providing control specimens with the SYK/ITK translocation and Ms Monica Kramer and Ms Carrie Stevenson for administrative assistance.",

year = "2008",

month = jun,

doi = "10.1038/leu.2008.77",

language = "English (US)",

volume = "22",

pages = "1139--1143",

journal = "Leukemia",

issn = "0887-6924",

publisher = "Nature Publishing Group",

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T1 - Overexpression of Syk tyrosine kinase in peripheral T-cell lymphomas

AU - Feldman, A. L.

AU - Sun, D. X.

AU - Law, M. E.

AU - Novak, A. J.

AU - Attygalle, A. D.

AU - Thorland, E. C.

AU - Fink, S. R.

AU - Vrana, J. A.

AU - Caron, B. L.

AU - Morice, W. G.

AU - Remstein, E. D.

AU - Grogg, K. L.

AU - Kurtin, P. J.

AU - Macon, W. R.

AU - Dogan, A.

N1 - Funding Information: We acknowledge the support from the Iowa/Mayo Lymphoma SPORE grant from the National Cancer Institute (P50 CA97274). In addition, we thank Ms Connie Lesnick for help with flow cytometry, Dr B Streubel for providing control specimens with the SYK/ITK translocation and Ms Monica Kramer and Ms Carrie Stevenson for administrative assistance.

PY - 2008/6

Y1 - 2008/6

N2 - 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.

AB - 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.

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Overexpression of Syk tyrosine kinase in peripheral T-cell lymphomas

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