Tawana K et al, 2015 Blood
Link to abstract: http://www.bloodjournal.org/content/126/10/1214
24 individuals from 10 families with CEBPA germline mutations and AML had whole-exome (WES) and deep sequencing on leukemic cells. The results showed that germline CEBPA mutations clustered within the N-terminal and were highly penetrant, with AML presenting at a median age of 24.5 years (range, 1.75-46 years). In all diagnostic tumors tested (n = 18), a second CEBPA mutation was detected, with the acquired (somatic) mutations preferentially targeting the C-terminal. Deep sequencing of diagnostic and relapse paired samples suggested that recurrence was triggered by novel, independent clones with different CEBPA mutations than at presentation. The cumulative incidence of relapse in patients with this syndrome was 56% at 10 years (n = 11), and 3 patients experienced ≥3 disease episodes over a period of 17 to 20 years; still, long-term overall survival was favorable (10-year overall survival, 67%).
*In conclusion, this article states that relapse in patients with germline CEBPA mutatuion is due to additional novel mutations and not recurrence of the initially seen one and that treatment for relapse might therefore be more successful than in other types of leukemia as shown by the relatively good survival rate.