期刊
LEUKEMIA
卷 23, 期 8, 页码 1374-1377出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/leu.2009.75
关键词
T-ALL; glucocorticoid resistance; gamma-secretase inhibitor; NOTCH1; Gastrointestinal toxicity
资金
- NIH [R01CA120196, R01CA129382]
- Leukemia and Lymphoma Society [1287-08, 6237-08]
- Fondo de Investigacion Sanitaria [CD07/00033]
Inhibition of NOTCH1 signaling with gamma-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. Leukemia (2009) 23, 1374-1377; doi:10.1038/leu.2009.75; published online 9 April 2009
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