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SATB1 in Malignant T Cells

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  • Simon Fredholm
  • Andreas Willerslev-Olsen
  • Özcan Met
  • Linda Kubat
  • Maria Gluud
  • Sarah L Mathiasen
  • Christina Friese
  • Edda Blümel
  • David L Petersen
  • Tengpeng Hu
  • Claudia Nastasi
  • Lise M Lindahl
  • Terkild B Buus
  • Thorbjørn Krejsgaard
  • Mariusz A Wasik
  • Katharina L Kopp
  • Sergei B Koralov
  • Jenny L Persson
  • Charlotte M Bonefeld
  • Carsten Geisler
  • Anders Woetmann
  • Lars Iversen
  • Jürgen C Becker
  • Niels Ødum
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Deficient expression of SATB1 hampers thymocyte development and results in inept T-cell lineages. Recent data implicate dysregulated SATB1 expression in the pathogenesis of mycosis fungoides, the most frequent variant of cutaneous T-cell lymphoma. Here, we report on a disease stage-associated decrease of SATB1 expression and an inverse expression of STAT5 and SATB1 in situ. STAT5 inhibited SATB1 expression through induction of microRNA-155. Decreased SATB1 expression triggered enhanced expression of IL-5 and IL-9 (but not IL-6 and IL-32), whereas increased SATB1 expression had the opposite effect, indicating that the microRNA-155 target SATB1 is a repressor of IL-5 and IL-9 in malignant T cells. In accordance, inhibition of STAT5 and its upstream activator JAK3 triggered increased SATB1 expression and a concomitant suppression of IL-5 and IL-9 expression in malignant T cells. In conclusion, we provide a mechanistic link between the proto-oncogenic JAK3/STAT5/microRNA-155 pathway, SATB1, and cytokines linked to CTCL severity and progression, indicating that SATB1 dysregulation is involved in cutaneous T-cell lymphoma pathogenesis.

Original languageEnglish
JournalThe Journal of investigative dermatology
Volume138
Issue number8
Pages (from-to)1805-1815
Number of pages11
ISSN0022-202X
DOIs
Publication statusPublished - Aug 2018

ID: 56258927