Selective gamma-secretase targeting for NOTCH induced T cell acute lymphoblastic leukemia KU Leuven
NOTCH1 heterodimerization (HD) domain mutations are found at high frequency in T cell acute lymphoblastic leukemia (T-ALL). These mutant NOTCH1 receptors are constitutively cleaved by the gamma-secretase (GS) complex, independent of ligand, resulting in continuous NOTCH signaling. The key role for NOTCH in T-ALL resulted in a search for molecules targeting NOTCH. Gammasecretase inhibitors (GSIs) inhibit the proteolytic activity of the GS ...