NOTCH1 and acute lymphoblastic leukemia: Another similar mechanism of constitutive Notch1 signaling, known as juxta-membrane expansion (JME), present in 3% of T-ALL, is due to in-frame insertion mutations in exon 28 that displace the HD-LNR complex away from the cell membrane, inducing a conformational change that allows for increased ADAM cleavage [62].