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

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.

SUBMITTER: Krejsgaard T

PROVIDER: S-EPMC2700325 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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

Krejsgaard Thorbjørn T 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

Blood 20090407 23

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 3 ...[more]

PMID: 19351960

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Project description:AimRecent studies suggested a role for IL31 in the pathogenesis of pruritus and disease severity in patients with cutaneous T cell lymphomas (CTCL). However, discrepant results were reported for IL31 serum levels, transcriptional expression levels or immunohistochemistry studies and its relation to pruritus intensity and/or disease severity in CTCL. Most studies did not distinguish between different CTCL variants. We investigated IL31 serum levels in different subtypes of CTCL, including Mycosis Fungoides (MF) (typically not pruritic), Folliculotropic Mycosis Fungoides (FMF) and Sézary syndrome (SS) (both often pruritic).MethodsFrom 54 CTCL patients (17 SS, 21 FMF and 16 classic MF) serum samples were analyzed with a high sensitivity V-PLEX immunoassay for IL31. The study group included 35/54 (65%) patients with complaints of pruritus. Thirty-five patients had advanced stage disease (≥stage IIB). A visual analog scale score (VAS score) for pruritus was available in 29 CTCL patients (7 SS, 9 FMF and 13 classic MF) and in other cases complaints of pruritus were retrieved from medical records. qPCR analyses for IL31 expression were performed in lesional skin biopsies from 8 CTCL patients. Serum samples from 4 healthy individuals without pruritus and from 5 atopic dermatitis (AD) patients with severe pruritus were included as controls.ResultsIn 11/54 (20%) of CTCL patients low serum levels of IL31 were detected (mean 0.48 pg/mL, range 0.20-1.39 pg/mL) including 6/17 (35%) SS patients (mean 0.57 pg/mL) and 5/21 (24%) FMF patients (mean 0.33 pg/mL). All 11 patients with detectable levels of IL31 reported complaints of moderate to severe pruritus and 9/11 patients presented with advanced stage disease (≥IIB). qPCR analyses resulted in lowly expressed IL31 expression levels in 4 of 8 patients; these patients all suffered from pruritus and advanced stage disease.ConclusionsTranslational and transcriptional expression levels of IL31 were very low or undetectable in CTCL patients. Detectable low IL31 serum levels were exclusively observed in SS and FMF patients and not in patients with classic MF. However, these marginal IL31 levels in a small proportion of CTCL patients do not support an essential role for IL31 in CTCL patients.

Dataset Information

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

Publications

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

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