title: CEBPA gene mutations in Egyptian acute myeloid leukemia patients: impact on prognosis.
abstract: OBJECTIVE
  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.
  
  
  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 (CEBPA(double-mut)) as well as five cases with only one single heterozygous mutation (CEBPA(single-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 CEBPA(single-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).
  
  
  CONCLUSIONS
  CEBPA mutation status is known to be a prognostic factor for favorable outcome in AML patients. CEBPA(double-mut) is associated with favorable DFS and OS. In contrast, CEBPA(single-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 CEBPA(double-mut) should be clearly defined from CEBPA(single-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.
authors.affiliation: Hematology Unit, Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Awad
authors.forename: Doaa A
authors.initials: DA
authors.lastname: Aladle
authors.forename: Nashwa K
authors.initials: NK
authors.lastname: Abousamra
authors.forename: Doaa M
authors.initials: DM
authors.lastname: Elghannam
authors.forename: Iman M
authors.initials: IM
authors.lastname: Fawzy
mesh_terms: D000328:Adult; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D004534:Egypt; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D059785:Karyotype; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics*; D015479:Leukemia, Myelomonocytic, Acute / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human