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

Thorbjørn Krejsgaard; Claudia S Vetter-Kauczok; Anders Woetmann; Hermann Kneitz; Karsten W Eriksen; Paola Lovato; Qian Zhang; Mariusz A Wasik; Carsten Geisler; Elisabeth Ralfkiaer; Juergen C Becker; Niels Odum

doi:10.1182/blood-2008-09-181024

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

Thorbjørn Krejsgaard, Claudia S Vetter-Kauczok, Anders Woetmann, Hermann Kneitz, Karsten W Eriksen, Paola Lovato, Qian Zhang, Mariusz A Wasik, Carsten Geisler, Elisabeth Ralfkiaer, Juergen C Becker, Niels Odum

45 Citations (Scopus)

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.

Original language	English
Journal	Blood
Volume	113
Issue number	23
Pages (from-to)	5896-904
Number of pages	8
ISSN	0006-4971
DOIs	https://doi.org/10.1182/blood-2008-09-181024
Publication status	Published - 2009

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10.1182/blood-2008-09-181024

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@article{1dd840e096cc11de8bc9000ea68e967b,

title = "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.",

author = "Thorbj{\o}rn Krejsgaard and Vetter-Kauczok, {Claudia S} and Anders Woetmann and Hermann Kneitz and Eriksen, {Karsten W} and Paola Lovato and Qian Zhang and Wasik, {Mariusz A} and Carsten Geisler and Elisabeth Ralfkiaer and Becker, {Juergen C} and Niels Odum",

note = "Keywords: Cell Line; Cell Proliferation; Enzyme Activation; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Longitudinal Studies; Lymphoma, T-Cell, Cutaneous; NF-kappa B; Neoplasm Staging; STAT3 Transcription Factor; Skin Neoplasms; src-Family Kinases",

year = "2009",

doi = "10.1182/blood-2008-09-181024",

language = "English",

volume = "113",

pages = "5896--904",

journal = "Blood",

issn = "0006-4971",

publisher = "American Society of Hematology",

number = "23",

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TY - JOUR

T1 - Ectopic expression of B-lymphoid kinase in cutaneous T-cell lymphoma

AU - Krejsgaard, Thorbjørn

AU - Vetter-Kauczok, Claudia S

AU - Woetmann, Anders

AU - Kneitz, Hermann

AU - Eriksen, Karsten W

AU - Lovato, Paola

AU - Zhang, Qian

AU - Wasik, Mariusz A

AU - Geisler, Carsten

AU - Ralfkiaer, Elisabeth

AU - Becker, Juergen C

AU - Odum, Niels

N1 - Keywords: Cell Line; Cell Proliferation; Enzyme Activation; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Longitudinal Studies; Lymphoma, T-Cell, Cutaneous; NF-kappa B; Neoplasm Staging; STAT3 Transcription Factor; Skin Neoplasms; src-Family Kinases

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

U2 - 10.1182/blood-2008-09-181024

DO - 10.1182/blood-2008-09-181024

M3 - Journal article

C2 - 19351960

SN - 0006-4971

VL - 113

SP - 5896

EP - 5904

JO - Blood

JF - Blood

IS - 23

ER -

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

Abstract

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