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
Bloodjournal_title
Bloodauthors
Kamstrup MR,Gjerdrum LM,Biskup E,Lauenborg BT,Ralfkiaer E,Woetmann A,Ødum N,Gniadecki Rdoi
10.1182/blood-2009-12-260216subject
Has Abstractpub_date
2010-10-07 00:00:00pages
2504-12issue
14eissn
0006-4971issn
1528-0020pii
blood-2009-12-260216journal_volume
116pub_type
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