Therefore, the seminal discovery in 2004 that more than 60% of T-ALLs carry NOTCH1 gain-of-function (GOF) somatic mutations that also generate a truncated and constitutively active receptor caused an immense revolution in the field, pointing to NOTCH1 as a key regulator of T-ALL pathogenesis [37]. Here, NOTCH1 is linked to T-cell acute lymphoblastic leukemia.