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

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

Leukemia

journal_title

Leukemia

authors

Real PJ,Ferrando AA

doi

10.1038/leu.2009.75

subject

Has Abstract

pub_date

2009-08-01 00:00:00

pages

1374-7

issue

8

eissn

0887-6924

issn

1476-5551

pii

leu200975

journal_volume

23

pub_type

杂志文章,评审

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