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Leukemia. 2009 Aug;23(8):1374-7. doi: 10.1038/leu.2009.75. Epub 2009 Apr 9.

NOTCH inhibition and glucocorticoid therapy in T-cell acute lymphoblastic leukemia.

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1
Institute for Cancer Genetics, Columbia University, New York, NY 10032, USA.

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.

PMID:
19357700
PMCID:
PMC2814171
DOI:
10.1038/leu.2009.75
[Indexed for MEDLINE]
Free PMC Article

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