Abstract:
: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-kappaB)-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.
journal_name
Bloodjournal_title
Bloodauthors
Krejsgaard T,Vetter-Kauczok CS,Woetmann A,Kneitz H,Eriksen KW,Lovato P,Zhang Q,Wasik MA,Geisler C,Ralfkiaer E,Becker JC,Ødum Ndoi
10.1182/blood-2008-09-181024subject
Has Abstractpub_date
2009-06-04 00:00:00pages
5896-904issue
23eissn
0006-4971issn
1528-0020pii
blood-2008-09-181024journal_volume
113pub_type
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