Most of the HD domain mutations were located within the HD-N region (n = 58), whereas HD-C mutations were less common (n = 11). The HD-N domain mutations were clustered in “hot spots” spanning amino acid residues 1574 to 1602 (n = 48) and 1606 to 1638 (n = 12) (Figure 1A). The HD-C domain mutations were located in a region spanning amino acid residues 1674 to 1723 (Figure 1B). Thirty-one of 58 of the HD-N mutations and 6 of 11 of the HD-C mutations introduced Pro-residues into the protein (Figure 1A-B)....Furthermore, in a multivariate analysis, including variables known to be associated with prednisone response (sex, age at diagnosis, presenting WBC count at diagnosis, and T-cell immunophenotype), the NOTCH1 mutation status retained its significant effect on early response to treatment...Patients with NOTCH1 mutations showed a significantly better relapse-free survival compared with those without mutations (90% vs 71%, P = .004).