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

Authors :
Hu, Tengpeng
Krejsgaard, Thorbjørn
Nastasi, Claudia
Buus, Terkild Brink
Nansen, Anneline
Hald, Andreas
Spee, Pieter
Nielsen, Pia Rude
Blümel, Edda
Gluud, Maria
Willerslev-Olsen, Andreas
Woetmann, Anders
Bzorek, Michael
Eriksen, Jens O.
Ødum, Niels
Rahbek Gjerdrum, Lise Mette
Buus, Terkild Brink
Nielsen, Pia Rude
Eriksen, Jens O
Rahbek Gjerdrum, Lise Mette
Source :
Dermatology (10188665); 2020, Vol. 236 Issue 2, p123-132, 10p, 1 Color Photograph, 2 Charts, 4 Graphs
Publication Year :
2020

Abstract

<bold>Background: </bold>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.<bold>Objectives: </bold>This study aims to examine the expression of Kv1.3 in situ and in vitro in CTCL.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>We provide the first evidence of a heterogeneous Kv1.3 expression in situ in CTCL lesions. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
10188665
Volume :
236
Issue :
2
Database :
Complementary Index
Journal :
Dermatology (10188665)
Publication Type :
Academic Journal
Accession number :
142975918
Full Text :
https://doi.org/10.1159/000502137