Overexpression of Syk tyrosine kinase in peripheral T-cell lymphomas

被引：109

作者：

Feldman, A. L. ^{[1
]}

Sun, D. X. ^{[1
]}

Law, M. E. ^{[1
]}

Novak, A. J. ^{[2
]}

Attygalle, A. D. ^{[3
]}

Thorland, E. C. ^{[1
]}

Fink, S. R. ^{[1
]}

Vrana, J. A. ^{[1
]}

Caron, B. L. ^{[1
]}

Morice, W. G. ^{[1
]}

Remstein, E. D. ^{[1
]}

Grogg, K. L. ^{[1
]}

Kurtin, P. J. ^{[1
]}

Macon, W. R. ^{[1
]}

Dogan, A. ^{[1
]}

机构：

[1] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA

[2] Mayo Clin, Dept Hematol, Rochester, MN 55905 USA

[3] Royal Marsden Hosp, Dept Histopathol, London SW3 6JJ, England

来源：

LEUKEMIA | 2008年 / 22卷 / 06期

关键词：

peripheral T-cell lymphoma; Syk; tyrosine kinase; phosphorylation;

D O I：

10.1038/leu.2008.77

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：1139 / 1143

页数：5

共 25 条

[1] Functional role for Syk tyrosine kinase in natural killer cell-mediated natural cytotoxicity [J].

Brumbaugh, KM ;

Binstadt, BA ;

Billadeau, DD ;

Schoon, RA ;

Dick, CJ ;

Ten, RM ;

Leibson, PJ .

JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 186 (12) :1965-1974

[2] Differential regulation by leukotrienes and calcium of Fcγ receptor-induced phagocytosis and Syk activation in dendritic cells versus macrophages [J].

Canetti, Claudio ;

Aronoff, David M. ;

Choe, Mun ;

Flamand, Nicolas ;

Wettlaufer, Scott ;

Toews, Galen B. ;

Chen, Gwo-Hsiao ;

Peters-Golden, Marc .

JOURNAL OF LEUKOCYTE BIOLOGY, 2006, 79 (06) :1234-1241

[3]

CHAN AC, 1994, J IMMUNOL, V152, P4758

[4] SYK-dependent tonic B-cell receptor signaling is a rational treatment target in diffuse large B-cell lymphoma [J].

Chen, Linfeng ;

Monti, Stefano ;

Juszczynski, Przemyslaw ;

Daley, John ;

Chen, Wen ;

Witzig, Thomas E. ;

Habermann, Thomas M. ;

Kutok, Jeffery L. ;

Shipp, Margaret A. .

BLOOD, 2008, 111 (04) :2230-2237

[5] Peripheral T-cell lymphoma with follicular involvement and a CD4+/bcl-6+phenotype [J].

de Leval, L ;

Savilo, E ;

Longtine, J ;

Ferry, JA ;

Harris, NL .

AMERICAN JOURNAL OF SURGICAL PATHOLOGY, 2001, 25 (03) :395-400

[6] Prognostic factors and treatment of patients with T-cell non-Hodgkin lymphoma -: The MD Anderson Cancer Center experience [J].

Escalón, MP ;

Liu, NS ;

Yang, Y ;

Hess, M ;

Smith, TL ;

Dang, NH .

CANCER, 2005, 103 (10) :2091-2098

[7] Spleen tyrosine kinase (Syk), a novel target of curcumin, is required for B lymphoma growth [J].

Gururajan, Murali ;

Dasu, Trivikram ;

Shahidain, Seif ;

Jennings, C. Darrell ;

Robertson, Darrell A. ;

Rangnekar, Vivek M. ;

Bondada, Subbarao .

JOURNAL OF IMMUNOLOGY, 2007, 178 (01) :111-121

[8] Altered B-cell receptor signaling kinetics distinguish human follicular lymphoma. B cells from tumor-infiltrating nonmalignant B cells [J].

Irish, Jonathan M. ;

Czerwinski, Debra K. ;

Nolan, Garry P. ;

Levy, Ronald .

BLOOD, 2006, 108 (09) :3135-3142

[9]

Jaffe ES, 2001, Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues, P189

[10] Syk-dependent mTOR activation in follicular lymphoma cells [J].

Leseux, Ludivine ;

Hamdi, Safouane M. ;

al Saati, Talal ;

Capilla, Florence ;

Recher, Christian ;

Laurent, Guy ;

Bezombes, Christine .

BLOOD, 2006, 108 (13) :4156-4162

← 1 2 3 →