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Updated: Jun 12, 2026
Flow Cytometry-based Assay for the Monitoring of NK Cell Functions
Published on: October 30, 2016
Notch signalling in primary cutaneous CD30+ lymphoproliferative disorders: a new therapeutic approach?
M R Kamstrup1, E Biskup, R Gniadecki
1Department of Dermatology, Bispebjerg Hospital, Bispebjerg bakke 23, Copenhagen 2400, Denmark.
Background:
The oncogenic potential of deregulated Notch signalling has been described in several haematopoietic malignancies. We have previously reported an increased expression of Notch1 in primary cutaneous CD30+ lymphoproliferative disorders, lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma (pcALCL).
Objectives:
To investigate the functional importance of Notch signalling in cell lines derived from pcALCL.
Methods:
Cell lines derived from pcALCL (Mac1, Mac2a and JK) were treated with different γ-secretase inhibitors (GSIs) (GSI I, IX, XX and XXI). The effects of GSIs on cell viability, apoptosis and cell cycle progression were measured as well as the impact of GSI I on the known prosurvival pathway Akt-mTOR-FOXO3a.
Results:
Notch family members were expressed in all investigated pcALCL cell lines. GSI I had a marked proapoptotic effect, but GSI IX, XX and XXI were much less potent. The GSI I-triggered apoptosis was preceded by an accumulation of cells in the G2/M, cyclin B1-controlled phase of the cell cycle accompanied by an increase in the cyclin-dependent kinase inhibitor, p21(WAF/Cip) . GSI I induced the nuclear translocation of proapoptotic FOXO3a, probably via an Akt-independent pathway.
Conclusions:
Notch signalling may be a future therapeutic target for the treatment of advanced pcALCL.
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