Ectopic expression of B-lymphoid kinase in cutaneous T-cell lymphoma.
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.
Krejsgaard
Thorbjørn
T
Department of Biology, University of Copenhagen, Copenhagen, Denmark
Vetter-Kauczok
Claudia S
CS
Woetmann
Anders
A
Kneitz
Hermann
H
Eriksen
Karsten W
KW
Lovato
Paola
P
Zhang
Qian
Q
Wasik
Mariusz A
MA
Geisler
Carsten
C
Ralfkiaer
Elisabeth
E
Becker
Juergen C
JC
Ødum
Niels
N
D002460:Cell Line; D049109:Cell Proliferation; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008137:Longitudinal Studies; D016410:Lymphoma, T-Cell, Cutaneous / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D009367:Neoplasm Staging; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012878:Skin Neoplasms / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
D016328:NF-kappa B; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C082599:protein-tyrosine kinase p55(blk); D019061:src-Family Kinases