Expression of the Voltage-Gated Potassium Channel Kv1.3 in Lesional Skin from Patients with Cutaneous T-Cell Lymphoma and Benign Dermatitis

Tengpeng Hu; Thorbjørn Krejsgaard; Claudia Nastasi; Terkild Brink Buus; Anneline Nansen; Andreas Hald; Pieter Spee; Pia Rude Nielsen; Edda Blümel; Maria Gluud; Andreas Willerslev-Olsen; Anders Woetmann; Michael Bzorek; Jens O. Eriksen; Niels Ødum; Lise Mette Rahbek Gjerdrum

doi:10.1159/000502137

Expression of the Voltage-Gated Potassium Channel Kv1.3 in Lesional Skin from Patients with Cutaneous T-Cell Lymphoma and Benign Dermatitis

Tengpeng Hu, Thorbjørn Krejsgaard, Claudia Nastasi, Terkild Brink Buus, Anneline Nansen, Andreas Hald, Pieter Spee, Pia Rude Nielsen, Edda Blümel, Maria Gluud, Andreas Willerslev-Olsen, Anders Woetmann, Michael Bzorek, Jens O. Eriksen, Niels Ødum, Lise Mette Rahbek Gjerdrum^*

^*Corresponding author af dette arbejde

Institut for Klinisk Medicin

3 Citationer (Scopus)

Abstract

Background: The voltage-gated potassium channel Kv1.3 (KCNA3) is expressed by effector memory T cells (TEM) and plays an important role in their activation and proliferation. Mycosis fungoides (MF), the most common subtype of cutaneous T-cell lymphoma (CTCL), was recently proposed to be a malignancy of skin-resident TEM. However, the expression of Kv1.3 in CTCL has not been investigated. Objectives: This study aims to examine the expression of Kv1.3 in situ and in vitro in CTCL. Methods: The expression of Kv1.3 was examined by immunohistochemistry in skin lesions from 38 patients with MF, 4 patients with Sézary syndrome (SS), and 27 patients with benign dermatosis. In 4 malignant T-cell lines of CTCL (Myla2059, PB2B, SeAx, and Mac2a) and a non-malignant T-cell line (MyLa1850), the expression of Kv1.3 was determined by flow cytometry. The proliferation of those cell lines treated with various concentrations of Kv1.3 inhibitor ShK was measured by 3H-thymdine incorporation. Results: Half of the MF patients (19/38) displayed partial Kv1.3 expression including 1 patient with moderate Kv1.3 positivity, while the other half (19/38) exhibited Kv1.3 negativity. An almost identical distribution was observed in patients with benign conditions, that is, 44.4% (12/27) were partially positive for Kv1.3 including 1 patient with moderate Kv1.3 positivity, while 55.6% (15/27) were Kv1.3 negative. In contrast, 3 in 4 SS patients displayed partial Kv1.3 positivity including 2 patients with weak staining and 1 with moderate staining, while 1 in 4 SS patients was Kv1.3 negative. In addition, all malignant T-cell lines, and a non-malignant T-cell line, displayed low Kv1.3 surface expression with a similar pattern. Whereas 2 cell lines (PB2B and Mac2a) were sensitive to Kv1.3 blockade, the other 2 (Myla2059 and SeAx) were completely resistant. Conclusions: We provide the first evidence of a heterogeneous Kv1.3 expression in situ in CTCL lesions.

Originalsprog	Engelsk
Tidsskrift	Dermatology
ISSN	1018-8665
DOI	https://doi.org/10.1159/000502137
Status	Udgivet - 1 apr. 2020

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10.1159/000502137

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Hu, T., Krejsgaard, T., Nastasi, C., Buus, T. B., Nansen, A., Hald, A., Spee, P., Nielsen, P. R., Blümel, E., Gluud, M., Willerslev-Olsen, A., Woetmann, A., Bzorek, M., Eriksen, J. O., Ødum, N., & Rahbek Gjerdrum, L. M. (2020). Expression of the Voltage-Gated Potassium Channel Kv1.3 in Lesional Skin from Patients with Cutaneous T-Cell Lymphoma and Benign Dermatitis. Dermatology. https://doi.org/10.1159/000502137

Hu, T, Krejsgaard, T, Nastasi, C, Buus, TB, Nansen, A, Hald, A, Spee, P, Nielsen, PR, Blümel, E, Gluud, M, Willerslev-Olsen, A, Woetmann, A, Bzorek, M, Eriksen, JO, Ødum, N & Rahbek Gjerdrum, LM 2020, 'Expression of the Voltage-Gated Potassium Channel Kv1.3 in Lesional Skin from Patients with Cutaneous T-Cell Lymphoma and Benign Dermatitis', Dermatology. https://doi.org/10.1159/000502137

@article{fd11ec6ba5c948e0beaa4b34eb630e82,

title = "Expression of the Voltage-Gated Potassium Channel Kv1.3 in Lesional Skin from Patients with Cutaneous T-Cell Lymphoma and Benign Dermatitis",

abstract = "Background: The voltage-gated potassium channel Kv1.3 (KCNA3) is expressed by effector memory T cells (TEM) and plays an important role in their activation and proliferation. Mycosis fungoides (MF), the most common subtype of cutaneous T-cell lymphoma (CTCL), was recently proposed to be a malignancy of skin-resident TEM. However, the expression of Kv1.3 in CTCL has not been investigated. Objectives: This study aims to examine the expression of Kv1.3 in situ and in vitro in CTCL. Methods: The expression of Kv1.3 was examined by immunohistochemistry in skin lesions from 38 patients with MF, 4 patients with S{\'e}zary syndrome (SS), and 27 patients with benign dermatosis. In 4 malignant T-cell lines of CTCL (Myla2059, PB2B, SeAx, and Mac2a) and a non-malignant T-cell line (MyLa1850), the expression of Kv1.3 was determined by flow cytometry. The proliferation of those cell lines treated with various concentrations of Kv1.3 inhibitor ShK was measured by 3H-thymdine incorporation. Results: Half of the MF patients (19/38) displayed partial Kv1.3 expression including 1 patient with moderate Kv1.3 positivity, while the other half (19/38) exhibited Kv1.3 negativity. An almost identical distribution was observed in patients with benign conditions, that is, 44.4% (12/27) were partially positive for Kv1.3 including 1 patient with moderate Kv1.3 positivity, while 55.6% (15/27) were Kv1.3 negative. In contrast, 3 in 4 SS patients displayed partial Kv1.3 positivity including 2 patients with weak staining and 1 with moderate staining, while 1 in 4 SS patients was Kv1.3 negative. In addition, all malignant T-cell lines, and a non-malignant T-cell line, displayed low Kv1.3 surface expression with a similar pattern. Whereas 2 cell lines (PB2B and Mac2a) were sensitive to Kv1.3 blockade, the other 2 (Myla2059 and SeAx) were completely resistant. Conclusions: We provide the first evidence of a heterogeneous Kv1.3 expression in situ in CTCL lesions.",

author = "Tengpeng Hu and Thorbj{\o}rn Krejsgaard and Claudia Nastasi and Buus, {Terkild Brink} and Anneline Nansen and Andreas Hald and Pieter Spee and Nielsen, {Pia Rude} and Edda Bl{\"u}mel and Maria Gluud and Andreas Willerslev-Olsen and Anders Woetmann and Michael Bzorek and Eriksen, {Jens O.} and Niels {\O}dum and {Rahbek Gjerdrum}, {Lise Mette}",

year = "2020",

month = apr,

day = "1",

doi = "10.1159/000502137",

language = "English",

journal = "Dermatology",

issn = "1018-8665",

publisher = "S Karger AG",

}

TY - JOUR

T1 - Expression of the Voltage-Gated Potassium Channel Kv1.3 in Lesional Skin from Patients with Cutaneous T-Cell Lymphoma and Benign Dermatitis

AU - Hu, Tengpeng

AU - Krejsgaard, Thorbjørn

AU - Nastasi, Claudia

AU - Buus, Terkild Brink

AU - Nansen, Anneline

AU - Hald, Andreas

AU - Spee, Pieter

AU - Nielsen, Pia Rude

AU - Blümel, Edda

AU - Gluud, Maria

AU - Willerslev-Olsen, Andreas

AU - Woetmann, Anders

AU - Bzorek, Michael

AU - Eriksen, Jens O.

AU - Ødum, Niels

AU - Rahbek Gjerdrum, Lise Mette

PY - 2020/4/1

Y1 - 2020/4/1

N2 - Background: The voltage-gated potassium channel Kv1.3 (KCNA3) is expressed by effector memory T cells (TEM) and plays an important role in their activation and proliferation. Mycosis fungoides (MF), the most common subtype of cutaneous T-cell lymphoma (CTCL), was recently proposed to be a malignancy of skin-resident TEM. However, the expression of Kv1.3 in CTCL has not been investigated. Objectives: This study aims to examine the expression of Kv1.3 in situ and in vitro in CTCL. Methods: The expression of Kv1.3 was examined by immunohistochemistry in skin lesions from 38 patients with MF, 4 patients with Sézary syndrome (SS), and 27 patients with benign dermatosis. In 4 malignant T-cell lines of CTCL (Myla2059, PB2B, SeAx, and Mac2a) and a non-malignant T-cell line (MyLa1850), the expression of Kv1.3 was determined by flow cytometry. The proliferation of those cell lines treated with various concentrations of Kv1.3 inhibitor ShK was measured by 3H-thymdine incorporation. Results: Half of the MF patients (19/38) displayed partial Kv1.3 expression including 1 patient with moderate Kv1.3 positivity, while the other half (19/38) exhibited Kv1.3 negativity. An almost identical distribution was observed in patients with benign conditions, that is, 44.4% (12/27) were partially positive for Kv1.3 including 1 patient with moderate Kv1.3 positivity, while 55.6% (15/27) were Kv1.3 negative. In contrast, 3 in 4 SS patients displayed partial Kv1.3 positivity including 2 patients with weak staining and 1 with moderate staining, while 1 in 4 SS patients was Kv1.3 negative. In addition, all malignant T-cell lines, and a non-malignant T-cell line, displayed low Kv1.3 surface expression with a similar pattern. Whereas 2 cell lines (PB2B and Mac2a) were sensitive to Kv1.3 blockade, the other 2 (Myla2059 and SeAx) were completely resistant. Conclusions: We provide the first evidence of a heterogeneous Kv1.3 expression in situ in CTCL lesions.

AB - Background: The voltage-gated potassium channel Kv1.3 (KCNA3) is expressed by effector memory T cells (TEM) and plays an important role in their activation and proliferation. Mycosis fungoides (MF), the most common subtype of cutaneous T-cell lymphoma (CTCL), was recently proposed to be a malignancy of skin-resident TEM. However, the expression of Kv1.3 in CTCL has not been investigated. Objectives: This study aims to examine the expression of Kv1.3 in situ and in vitro in CTCL. Methods: The expression of Kv1.3 was examined by immunohistochemistry in skin lesions from 38 patients with MF, 4 patients with Sézary syndrome (SS), and 27 patients with benign dermatosis. In 4 malignant T-cell lines of CTCL (Myla2059, PB2B, SeAx, and Mac2a) and a non-malignant T-cell line (MyLa1850), the expression of Kv1.3 was determined by flow cytometry. The proliferation of those cell lines treated with various concentrations of Kv1.3 inhibitor ShK was measured by 3H-thymdine incorporation. Results: Half of the MF patients (19/38) displayed partial Kv1.3 expression including 1 patient with moderate Kv1.3 positivity, while the other half (19/38) exhibited Kv1.3 negativity. An almost identical distribution was observed in patients with benign conditions, that is, 44.4% (12/27) were partially positive for Kv1.3 including 1 patient with moderate Kv1.3 positivity, while 55.6% (15/27) were Kv1.3 negative. In contrast, 3 in 4 SS patients displayed partial Kv1.3 positivity including 2 patients with weak staining and 1 with moderate staining, while 1 in 4 SS patients was Kv1.3 negative. In addition, all malignant T-cell lines, and a non-malignant T-cell line, displayed low Kv1.3 surface expression with a similar pattern. Whereas 2 cell lines (PB2B and Mac2a) were sensitive to Kv1.3 blockade, the other 2 (Myla2059 and SeAx) were completely resistant. Conclusions: We provide the first evidence of a heterogeneous Kv1.3 expression in situ in CTCL lesions.

U2 - 10.1159/000502137

DO - 10.1159/000502137

M3 - Journal article

C2 - 31536992

AN - SCOPUS:85072524565

SN - 1018-8665

JO - Dermatology

JF - Dermatology

ER -

Expression of the Voltage-Gated Potassium Channel Kv1.3 in Lesional Skin from Patients with Cutaneous T-Cell Lymphoma and Benign Dermatitis

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