Abstract:
: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.
journal_name
Leukemiajournal_title
Leukemiaauthors
Real PJ,Ferrando AAdoi
10.1038/leu.2009.75subject
Has Abstractpub_date
2009-08-01 00:00:00pages
1374-7issue
8eissn
0887-6924issn
1476-5551pii
leu200975journal_volume
23pub_type
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