OBJECTIVETo investigate the incidence, molecular features and clinical significance of CCAAT/enhancer binding protein alpha (CEBPA) gene mutation in patients with acute myeloid leukemia (AML).

METHODSMutation analysis of the entire coding region of CEBPA gene in 206 de novo AML patients was performed by using polymerase chain reaction (PCR) followed by sequence analysis and fragment length analysis.

RESULTSOf 206 AML patients, 31 (15%) had CEBPA gene mutations, including 23 with double mutations (duCEBPA) and 8 with single mutation (siCEBPA). CEBPA gene mutations presented mainly in M2 subtype or intermediate risk patients. As compared with those with wild type CEBPA gene, patients with mutated CEBPA gene were of higher white blood cell counts [20.92(0.86-351.43)× 10(9)//L vs 8.17(0.47-295.2) × 10(9)/L, P=0.003], higher hemoglobin levels [97.5(51-128) g/L vs 80.5(13-153) g/L, P=0.015] and lower platelet counts [27.5(5-81)× 10(9)//L vs 44(3-548)× 10(9)/L, P=0.004]. Patients with CEBPA gene mutation had higher complete remission (CR) rate than those with wild type (P=0.009). While co-existing of NPM1 and siCEBPA mutations was observed in M5 subtype (2/8, 25%), NPM1 gene mutation was not present in any patients with duCEBPA mutation (0/23, 0%). Dynamic tracking analysis showed that CEBPA mutations disappeared at CR, and the same mutations re-appeared at relapse. When compared to sequence analysis, the coincidence rate of CEBPA mutations detected by fragment length analysis was 100% (54/54).

CONCLUSIONCEBPA gene mutation is a recurring genetic change in AML patients and has a certain correlation with clinical and laboratory features. It could be reliably used as a potential marker for minimal residual disease follow up. The prognostic significance of co-existing of siCEBPA with NPM1 mutations in patients with AML-M5 subtype needs further investigation.