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
N1 - � 2019 S. Karger AG, Basel.
PY - 2020/4
Y1 - 2020/4
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.
KW - Mycosis fungoides
KW - Kv1
KW - 3 channel
KW - ShK
KW - Cutaneous T-cell lymphoma
KW - Dermatitis
U2 - 10.1159/000502137
DO - 10.1159/000502137
M3 - Article
C2 - 31536992
VL - 236
SP - 123
EP - 132
JO - Dermatology
JF - Dermatology
SN - 1018-8665
IS - 2
ER -