We evaluated concurrent gene mutations, clinical outcome, and gene expression signatures of CCAAT/enhancer binding protein alpha (CEBPA) double mutations (CEBPAdm) versus single mutations (CEBPAsm) in 1182 cytogenetically normal acute myeloid leukemia (AML) patients (16-60 years of age). We identified 151 (12.8%) patients with CEBPA mutations (91 CEBPAdmand 60 CEBPAsm). The incidence of germline mutations was 7% (5 of 71), including 3 C-terminal mutations. CEBPAdmpatients had a lower frequency of concurrent mutations than CEBPAsmpatients (P < .0001). Both, groups were associated with a favorable outcome compared with CEBPAwt(5-year overall survival [OS] 63% and 56% vs 39%; P < .0001 and P = .05, respectively). However, in multivariable analysis only CEBPAdmwas a prognostic factor for favorable OS outcome (hazard ratio [HR] 0.36, P < .0001; event-free survival, HR 0.41, P < .0001; relapse-free survival, HR 0.55, P = .001). Outcome in CEBPAsmis dominated by concurrent NPM1 and/or FLT3 internal tandem duplication mutations. Unsupervised and supervised GEP analyses showed that CEBPAdmAML (n = 42), but not CEBPAsmAML (n = 18), expressed a unique gene signature. A 25-probe set prediction signature for CEBPAdmAML showed 100% sensitivity and specificity. Based on these findings, we propose that CEBPAdmshould be clearly defined from CEBPAsmAML and considered as a separate entity in the classification of AML.

doi.org/10.1182/blood-2010-09-307280, hdl.handle.net/1765/33529
Erasmus MC: University Medical Center Rotterdam

Taskesen, E., Bullinger, L., Corbacioglu, A., Sanders, M., Erpelinck, C., Wouters, B., … Valk, P. (2011). Prognostic impact, concurrent genetic mutations, and gene expression features of AML with CEBPA mutations in a cohort of 1182 cytogenetically normal AML patients: Further evidence for CEBPA double mutant AML as a distinctive disease entity. Blood, 117(8), 2469–2475. doi:10.1182/blood-2010-09-307280