NOTCH inhibition and glucocorticoid therapy in T-cell acute lymphoblastic leukemia
- 9 April 2009
- journal article
- review article
- Published by Springer Science and Business Media LLC in Leukemia
- Vol. 23 (8), 1374-1377
- https://doi.org/10.1038/leu.2009.75
Abstract
Inhibition of NOTCH1 signaling with γ-secretase inhibitors (GSIs) has been proposed as a molecularly targeted therapy in T-cell acute lymphoblastic leukemia (T-ALL). However, GSIs seem to have limited antileukemic activity in human T-ALL and are associated with severe gastrointestinal toxicity resulting from inhibition of NOTCH signaling in the gut. Inhibition of NOTCH1 signaling in glucocorticoid-resistant T-ALL restored glucocorticoid sensitivity and co-treatment with glucocorticoids inhibited GSI-induced gut toxicity. Thus, combination therapies with GSIs plus glucocorticoids may offer a new opportunity for the use of anti-NOTCH1 therapies in human T-ALL.Keywords
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