<i>CEBPA</i> mutation in acute myeloid leukemia: prognostic impact of bZIP domain mutation

Abstract One of the most important prognostic genes for acute myeloid leukemia (AML) is CEPBA , and its mutation (CEBPAmu) is present in nearly 10%–15% of de novo AML cases. CEBPAdm is associated with a favorable prognosis; however, CEBPAsm does not appear to have a better prognosis than CEBPAdm. We reviewed CEBPAmu-bZIP in 8694 cases across studies for prognostic impact in patients with de novo AML. It was observed that CEBPAmu in the basic leucine zipper domain (bZIP) was strongly associated with a favorable prognosis, but CEBPAmu out of the bZIP domain was not. CEBPA-bZIP mutations were discovered in 562 (6.46%) of 8694 cases, with 366 (65.1%) harboring a second CEBPA mutation (CEBPA-double-mutated [CEBPAdm]) and 196 (34.9%) having a single CEBPA-bZIP only mutation. Multivariate analysis of three studies consisting of 1028, 4708, and 2958 patients showed that CEBPAmu in bZIP was the most potent predictor of overall survival (OS) with overall survivability of 53%, 62%, and 89%, respectively, independently. However, complete remission of disease with bZIP mutation in the same studies was found to be 80%, 62%, and 78.6%, respectively. These findings indicate that CEBPAmu in bZIP is a potent marker for AML prognosis.