In chronic lymphocytic leukemia (CLL), ‘coding’ NOTCH1 mutations were initially detected in exon 34 where they result in truncation of the C-PEST regulatory protein sequence with consequent impaired degradation of the Notch1 intracellular domain (NCID), constitutive activation of Notch signalling and increased cell survival and resistance to apoptosis.1, 2, 3 Mutations occur in 6–10% of cases at diagnosis, with increasing prevalence in advanced disease stages, treatment-refractory disease and...
