CEBPA gene mutations in Egyptian acute myeloid leukemia patients: Impact on prognosis

Abstract

Aim: To assess the prognostic role of myeloid transcription factor gene CEBPA (CCAAT/enhancer binding protein-α), a novel gene involved in leukemia in Egyptian adults AML. Materials and Methods: Screening for CEBPA mutations was assessed using PCR-single-strand conformation polymorphism (PCR-SSCP) in pretreatment bone marrow samples from 55 newly diagnosed adult AML. Results: CEBPA mutations were found in 11 (20%) of 55 AML patients. They had significantly higher hemoglobin (P = 0.037), and lower LDH (P = 0.003) levels when compared to those without. CEBPA mutations were frequently detected in M4 (45.5%) and M2 (27.2%) subtypes, and significantly associated with normal karyotype (90.9%, P = 0.007). We distinguished six cases with two different mutations or one homozygous mutation (CEBPAdouble-mut) as well as five cases with only one single heterozygous mutation (CEBPAsingle-mut). Patients with CEBPA mutations had significantly higher complete remission (P = 0.047), lower mortality (p = 0.047). Double CEBPA mutant cases showed longer disease free survival (DFS) and overall survival (OS) when compared to wild type CEBPA (for DFS; median = 27 versus 24 months respectively; P = 0.009 and for OS; median = 28 versus 25 months respectively; p = 0.008). No significant differences were found between CEBPAsingle-mut cases and wild type cases regarding DFS and OS (for DFS; median = 13 versus 24 months respectively; P = 0.615 and for OS; median = 14 versus 25 months respectively; P = 0.703). Conclusion: CEBPA mutation status is known to be a prognostic factor for favorable outcome in AML patients. CEBPAdouble-mut is associated with favorable DFS and OS. In contrast, CEBPAsingle-mut AMLs survival studies did not differ significantly with wild-type cases. These results demonstrate significant underlying heterogeneity within CEBPA mutation positive AML with prognostic relevance. Based on these findings, we propose that CEBPAdouble-mut should be clearly defined from CEBPAsingle-mut AML and considered as a separate entity in the classification of AML. Furthermore, incorporation of CEBPA mutation status into novel risk-adapted therapeutic strategies in Egypt will improve the currently disappointing cure rate of this group of patients. © W. S. Maney & Son Ltd 2013.