Blood, 15 May 2005, Vol. 105, No. 10, pp. 4051-4059.
Prepublished online as a Blood First Edition Paper on January 27, 2005; DOI 10.1182/blood-2004-10-4008.
 Previous Article | Table of Contents | Next Article 
NEOPLASIA
Autocrine- and paracrine-activated receptor tyrosine kinases in classic Hodgkin lymphoma
Christoph Renné,
Klaus Willenbrock,
Ralf Küppers,
Martin-Leo Hansmann, and
Andreas Bräuninger
From the Department of Pathology and the Pharmazentrum Frankfurt, Institute of Clinical Pharmacology, University of Frankfurt, Germany; and the Institute for Cell Biology (Tumor Research), University of Duisburg–Essen, Essen, Germany.
The pathogenesis of Hodgkin lymphoma (HL) is still largely unknown. Based on a search for footprints of pathogenetic mechanisms in global RNA expression data of Hodgkin/Reed-Sternberg (HRS) cell lines, we analyzed the expression and activation of 6 receptor tyrosine kinases (RTKs) in classic HL. Immunohistochemistry revealed that the RTKs platelet-derived growth factor receptor A (PDGFRA), DDR2, EPHB1, RON, TRKB, and TRKA were each expressed in HRS cells in 30% to 75% of patients. These RTKs were not expressed in normal B cells, the origin of HRS cells, or in most B-cell non-Hodgkin lymphoma (NHL). In the majority of patients at least one RTK was expressed, and in most patients several RTKs were coexpressed, most prominently in Hodgkin lymphoma of the nodular sclerosis subtype. Phosphotyrosine-specific antibodies revealed exemplarily the activation of PDGFRA and TRKA/B and an elevation of cellular phosphotyrosine content. Immunohistochemistry for RTK ligands indicated that DDR2 and TRKA are likely activated in a paracrine fashion, whereas PDGFRA and EPHB1 seem to be activated by autocrine loops. Activating mutations were not detected in cDNA encoding the RTKs in HRS cell lines. These findings show the unprecedented coexpression of multiple RTKs in a tumor and indicate that aberrant RTK signaling is an important factor in HL pathogenesis and that it may be a novel therapeutic target.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
Related Article in Blood Online:
-
A role for RTKs in Hodgkin lymphoma
- Thomas Wirth
Blood 2005 105: 3766.
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
J. R. Flavell, K. R. N. Baumforth, V. H. J. Wood, G. L. Davies, W. Wei, G. M. Reynolds, S. Morgan, A. Boyce, G. L. Kelly, L. S. Young, et al.
Down-regulation of the TGF-beta target gene, PTPRK, by the Epstein-Barr virus encoded EBNA1 contributes to the growth and survival of Hodgkin lymphoma cells
Blood,
January 1, 2008;
111(1):
292 - 301.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G Kapatai and P Murray
Contribution of the Epstein Barr virus to the molecular pathogenesis of Hodgkin lymphoma
J. Clin. Pathol.,
December 1, 2007;
60(12):
1342 - 1349.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. R. Geiger and D. S. Peeper
Critical Role for TrkB Kinase Function in Anoikis Suppression, Tumorigenesis, and Metastasis
Cancer Res.,
July 1, 2007;
67(13):
6221 - 6229.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Nagel, C. Burek, L. Venturini, M. Scherr, H. Quentmeier, C. Meyer, A. Rosenwald, H. G. Drexler, and R. A. F. MacLeod
Comprehensive analysis of homeobox genes in Hodgkin lymphoma cell lines identifies dysregulated expression of HOXB9 mediated via ERK5 signaling and BMI1
Blood,
April 1, 2007;
109(7):
3015 - 3023.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Tedoldi, J. C. Paterson, M.-L. Hansmann, Y. Natkunam, T. Rudiger, P. Angelisova, M. Q. Du, H. Roberton, G. Roncador, L. Sanchez, et al.
Transmembrane adaptor molecules: a new category of lymphoid-cell markers
Blood,
January 1, 2006;
107(1):
213 - 221.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. E. Brown and N. R. Kamal
p-p70S6K (Thr 389) Expression in Nodular Sclerosing Hodgkin's Disease as Evidence for Receptor Tyrosine Kinase Signaling
Ann. Clin. Lab. Sci.,
October 1, 2005;
35(4):
413 - 414.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
