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Bispebjerg Hospital - a part of Copenhagen University Hospital
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Expression and function of Kv1.3 channel in malignant T cells in Sézary syndrome

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  • Tengpeng Hu
  • Terkild Brink Buus
  • Thorbjørn Krejsgaard
  • Anneline Nansen
  • Betina Kerstin Lundholt
  • Pieter Spee
  • Simon Fredholm
  • David Leander Petersen
  • Edda Blümel
  • Maria Gluud
  • Madalena N Monteiro
  • Andreas Willerslev-Olsen
  • Mads Hald Andersen
  • Per Thor Straten
  • Özcan Met
  • Veronica Stolearenco
  • Hanne Fogh
  • Robert Gniadecki
  • Claudia Nastasi
  • Thomas Litman
  • Anders Woetmann
  • Lise Mette Rahbek Gjerdrum
  • Niels Ødum
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The voltage-gated potassium channel Kv1.3 (KCNA3) is expressed by a subset of chronically activated memory T cells and plays an important role in their activation and proliferation. Here, we show that primary malignant T cells isolated from patients with Sézary syndrome (SS) express Kv1.3 and are sensitive to potent Kv1.3 inhibitors ShK and Vm24, but not sensitive to a less potent inhibitor [N17A/F32T]-AnTx. Kv1.3 blockade inhibits CD3/CD28-induced proliferation and IL-9 expression by SS cells in a concentration-dependent manner. In parallel, CD3/CD28-mediated CD25 induction is inhibited, whereas Kv1.3 blockade has no effect on apoptosis or cell death as judged by Annexin V and PI staining. In conclusion, we provide the first evidence that malignant T cells in SS express functional Kv1.3 channels and that Kv1.3 blockade inhibits activation-induced proliferation as well as cytokine and cytokine receptor expression in malignant T cells, suggesting that Kv1.3 is a potential target for therapy in SS.

Original languageEnglish
JournalOncotarget
Volume10
Issue number47
Pages (from-to)4894-4906
Number of pages13
ISSN1949-2553
DOIs
Publication statusPublished - 6 Aug 2019

ID: 58521676