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Notch1 as a potential therapeutic target in cutaneous T-cell lymphoma

Maria R Kamstrup1, Lise Mette Rahbek Gjerdrum, Edyta Biskup

  • 1Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark. mk43@bbh.regionh.dk

Blood
|June 12, 2010
PubMed

Insights

Notch signaling is implicated in cutaneous T-cell lymphoma. Inhibiting Notch1, particularly in advanced stages, induces apoptosis and may offer a novel therapeutic strategy for mycosis fungoides and Sézary syndrome.

Area of Science:

  • Oncology
  • Molecular Biology
  • Dermatology

Background:

  • Deregulation of Notch signaling is associated with T-cell leukemias and solid tumors.
  • The role of Notch signaling in mycosis fungoides and Sézary syndrome (cutaneous T-cell lymphoma subtypes) remains unclear.

Purpose of the Study:

  • To investigate the involvement of Notch signaling in the pathogenesis of mycosis fungoides and Sézary syndrome.
  • To explore the therapeutic potential of Notch signaling inhibition in cutaneous T-cell lymphoma.

Main Methods:

  • Immunohistochemistry was used to assess Notch1 expression in 40 skin biopsies from mycosis fungoides and Sézary syndrome patients.
  • The effects of a γ-secretase inhibitor and Notch1-specific siRNA on apoptosis were evaluated in cutaneous T-cell lymphoma cell lines and primary cells.

Main Results:

  • Prominent Notch1 expression was observed on tumor cells, increasing with disease stage.
  • Notch signaling inhibition, via γ-secretase inhibitor or Notch1 siRNA, induced significant apoptosis in mycosis fungoides and Sézary syndrome cells.
  • Apoptosis was mediated by the inhibition of the prosurvival nuclear factor-κB pathway.

Conclusions:

  • Notch signaling is active in cutaneous T-cell lymphoma.
  • Notch1 is a potential therapeutic target.
  • Inhibition of Notch signaling presents a promising new treatment strategy for cutaneous T-cell lymphoma.

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