The Open Leukemia Journal

2010, 3 : 9-15
Published online 2010 January 13. DOI: 10.2174/1876816401003010009
Publisher ID: TOLEUKEMIAJ-3-9

RESEARCH ARTICLE
 Malignant T Cells Exhibit CD45 Resistant Stat3 Activation and Proliferation in Cutaneous T-Cell Lymphoma

Thorbjørn Krejsgaard1,2 , Rikke Helvad1,2 , Elisabeth Ralfkiaer3 , Karen Astvad3,4 , Kirsten Grønbæk4 , Karsten W. Eriksen2 , Carsten Geisler2 , Katharina Kopp1,2 , Qian Zhang5 , Niels Odum1,2 and Anders Woetmann1,2, *
1 Department of Biology and 2Institute of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark
2 Institute of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark
3 Department of Pathology, University Hospital of Copenhagen, Copenhagen, Denmark
4 Department of Haematology, Rigshospitalet, Copenhagen, Denmark
5 Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA

* Address correspondence to this author at the Department of Biology and Institute of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark; Tel: +45 35 32 79 00; Fax: +45 35 32 78 68; E-mailawoetmann@sund.ku.dk

ABSTRACT

CD45 is a protein tyrosine phosphatase, which is well-known for regulating antigen receptor signalling in T and B cells via its effect on Src kinases. It has recently been shown that CD45 can also dephosphorylate Janus kinases (Jaks) and thereby regulate Signal transducer and activator of transcription (Stat) activation and cytokine-induced proliferation in lymphocytes. Consequently, CD45 dysregulation could be implicated in aberrant Jak/Stat activation and proliferation in lymphoproliferative diseases. Despite high expression of the CD45 ligand, Galectin-1, in skin lesions from cutaneous T-cell lymphoma (CTCL), the malignant T cells exhibit constitutive activation of the Jak3/Stat3 signalling pathway and uncontrolled proliferation. We show that CD45 expression is down-regulated on malignant T cells when compared to non-malignant T cells established from CTCL skin lesions. Moreover, CD45 cross-linking does not suppress the constitutive activation of Stat3 in the malignant T cells and there is no correlation between the level of activated Stat3 and the level of CD45 expression on the malignant T cells. Furthermore, in contrast to non-malignant T cells, the malignant T cells are protected against CD45-mediated inhibition of proliferation. In conclusion, our data suggest that CD45 dysregulation might play a role in the aberrant proliferation and Jak3/Stat3 activation in CTCL.

keywoards:

CD45, T cell lymphoma, CTCL, STAT, galectin.