Therapeutic targeting of NOTCH1 signaling in T-cell acute lymphoblastic leukemia
T Palomero, A Ferrando - Clinical Lymphoma and Myeloma, 2009 - Elsevier
The recent identification of activating mutations in NOTCH1 in the majority of T-cell acute
lymphoblastic leukemias (T-ALLs) has brought major interest toward targeting the NOTCH
signaling pathway in this disease. Small-molecule γ-secretase inhibitors (GSIs), which block
a critical proteolytic step required for NOTCH1 activation, can effectively block the activity of
NOTCH1 mutant alleles. However, the clinical development of GSIs has been hampered by
their low cytotoxicity against human T-ALL and the development of significant …
lymphoblastic leukemias (T-ALLs) has brought major interest toward targeting the NOTCH
signaling pathway in this disease. Small-molecule γ-secretase inhibitors (GSIs), which block
a critical proteolytic step required for NOTCH1 activation, can effectively block the activity of
NOTCH1 mutant alleles. However, the clinical development of GSIs has been hampered by
their low cytotoxicity against human T-ALL and the development of significant …