Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Krejsgaard, T; Vetter-Kauczok, CS; Woetmann, A; Kneitz, H; Eriksen, KW; Lovato, P; Zhang, Q; Wasik, MA; Geisler, C; Ralfkiaer, E; Becker, JC; Odum, N.
Ectopic expression of B-lymphoid kinase in cutaneous T-cell lymphoma.
Blood. 2009; 113(23):5896-5904
Doi: 10.1182/blood-2008-09-181024
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- Co-Autor*innen der Med Uni Graz
- Becker Jürgen Christian
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Cell Line -
- Cell Proliferation -
- Enzyme Activation -
- Gene Expression Regulation, Enzymologic -
- Gene Expression Regulation, Neoplastic -
- Humans -
- Longitudinal Studies -
- Lymphoma, T-Cell, Cutaneous - enzymology Lymphoma, T-Cell, Cutaneous - epidemiology Lymphoma, T-Cell, Cutaneous - genetics Lymphoma, T-Cell, Cutaneous - pathology
- NF-kappa B - metabolism
- Neoplasm Staging -
- STAT3 Transcription Factor - metabolism
- Skin Neoplasms - enzymology Skin Neoplasms - epidemiology Skin Neoplasms - genetics Skin Neoplasms - pathology
- src-Family Kinases - genetics src-Family Kinases - metabolism