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Blood, 4 June 2009, Vol. 113, No. 23, pp. 5896-5904.
Prepublished online as a Blood First Edition Paper on April 7, 2009; DOI 10.1182/blood-2008-09-181024.


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LYMPHOID NEOPLASIA

Ectopic expression of B-lymphoid kinase in cutaneous T-cell lymphoma

Thorbjørn Krejsgaard1,2, Claudia S. Vetter-Kauczok3, Anders Woetmann1,2, Hermann Kneitz3, Karsten W. Eriksen1,2, Paola Lovato1,2, Qian Zhang4, Mariusz A. Wasik4, Carsten Geisler2, Elisabeth Ralfkiaer5, Juergen C. Becker3, and Niels Ødum1,2

1 Department of Biology and 2 Institute of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark; 3 Department of Dermatology, Julius-Maximilians-University, Würzburg, Germany; 4 Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia; and 5 Department of Pathology, University Hospital of Copenhagen, Copenhagen, Denmark

B-lymphoid kinase (Blk) is exclusively expressed in B cells and thymocytes. Interestingly, transgenic expression of a constitutively active form of Blk in the T-cell lineage of mice results in the development of T-lymphoid lymphomas. Here, we demonstrate nuclear factor–kappa B (NF-{kappa}B)–mediated ectopic expression of Blk in malignant T-cell lines established from patients with cutaneous T-cell lymphoma (CTCL). Importantly, Blk is also expressed in situ in lesional tissue specimens from 26 of 31 patients with CTCL. Already in early disease the majority of epidermotropic T cells express Blk, whereas Blk expression is not observed in patients with benign inflammatory skin disorders. In a longitudinal study of an additional 24 patients biopsied for suspected CTCL, Blk expression significantly correlated with a subsequently confirmed diagnosis of CTCL. Blk is constitutively tyrosine phosphorylated in malignant CTCL cell lines and spontaneously active in kinase assays. Furthermore, targeting Blk activity and expression by Src kinase inhibitors and small interfering RNA (siRNA) inhibit the proliferation of the malignant T cells. In conclusion, this is the first report of Blk expression in CTCL, thereby providing new clues to the pathogenesis of the disease.


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