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Targeting Nuclear NOTCH2 by Gliotoxin Recovers a Tumor-Suppressor NOTCH3 Activity in CLL

Hubmann, Rainer ; Schnabl, Susanne ; Araghi, Mohammad ; Schmidl, Christian ; Rendeiro, André F. ; Hilgarth, Martin ; Demirtas, Dita ; Ali, Farghaly ; Staber, Philipp B. ; Valent, Peter ; Zielinski, Christoph ; Jäger, Ulrich ; Shehata, Medhat



Abstract

NOTCH signaling represents a promising therapeutic target in chronic lymphocytic leukemia (CLL). We compared the anti-neoplastic effects of the nuclear NOTCH2 inhibitor gliotoxin and the pan-NOTCH gamma-secretase inhibitor RO4929097 in primary CLL cells with special emphasis on the individual roles of the different NOTCH receptors. Gliotoxin rapidly induced apoptosis in all CLL cases tested, ...

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