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

Abstract:

:Deregulation of Notch signaling has been linked to the development of T-cell leukemias and several solid malignancies. Yet, it is unknown whether Notch signaling is involved in the pathogenesis of mycosis fungoides and Sézary syndrome, the most common subtypes of cutaneous T-cell lymphoma. By immunohistochemistry of 40 biopsies taken from skin lesions of mycosis fungoides and Sézary syndrome, we demonstrated prominent expression of Notch1 on tumor cells, especially in the more advanced stages. The γ-secretase inhibitor I blocked Notch signaling and potently induced apoptosis in cell lines derived from mycosis fungoides (MyLa) and Sézary syndrome (SeAx, HuT-78) and in primary leukemic Sézary cells. Specific down-regulation of Notch1 (but not Notch2 and Notch3) by siRNA induced apoptosis in SeAx. The mechanism of apoptosis involved the inhibition of nuclear factor-κB, which is the most important prosurvival pathway in cutaneous T-cell lymphoma. Our data show that Notch is present in cutaneous T-cell lymphoma and that its inhibition may provide a new way to treat cutaneous T-cell lymphoma.

journal_name

Blood

journal_title

Blood

authors

Kamstrup MR,Gjerdrum LM,Biskup E,Lauenborg BT,Ralfkiaer E,Woetmann A,Ødum N,Gniadecki R

doi

10.1182/blood-2009-12-260216

subject

Has Abstract

pub_date

2010-10-07 00:00:00

pages

2504-12

issue

14

eissn

0006-4971

issn

1528-0020

pii

blood-2009-12-260216

journal_volume

116

pub_type

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