The importance of Notch signaling in peripheral T-cell lymphomas

Maria Rørbæk Kamstrup, Edyta Biskup, Lise Mette Rahbek Gjerdrum, Elisabeth Ralfkiær, Omid Niazi, Robert Gniadecki

15 Citations (Scopus)

Abstract

Peripheral T-cell lymphomas (PTLs) represent an area of high medical need. Previously, we demonstrated high expression of Notch, a known oncogene, in primary cutaneous anaplastic large cell lymphoma (ALCL). In this study, we performed immunohistochemical staining for Notch1 in lymph nodes from PTL not otherwise specified (PTL-NOS) and systemic ALCL (ALK+ and ALK-) and report a similar distribution among the three subgroups: Negative, moderate and strong expression was, respectively, 18%, 27% and 55% for PTL-NOS (33 cases), 20%, 0% and 80% for ALCL ALK+ (10 cases) and 45%, 22% and 33% for ALCL ALK- (nine cases) (p > 0.05). In the ALK+ ALCL cell line, Karpas-299, pharmacological inhibition of Notch with γ-secretase inhibitor (GSI) I was far more potent than with GSI IX, XX and XXI with regard to cell viability and apoptosis. In conclusion, PTL tumor cells have prominent Notch1 expression and treatment with Notch inhibitors has cytotoxic effects.

Original languageEnglish
JournalLeukemia and Lymphoma
Volume55
Issue number3
Pages (from-to)639-44
Number of pages6
ISSN1042-8194
DOIs
Publication statusPublished - Mar 2014

Keywords

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Amyloid Precursor Protein Secretases
  • Apoptosis
  • Cell Cycle Checkpoints
  • Cell Line, Tumor
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Lymphoma, T-Cell, Peripheral
  • Male
  • Middle Aged
  • Oligopeptides
  • Receptor, Notch1
  • Receptors, Notch
  • Signal Transduction
  • Young Adult

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