Abstract:

Aim: The aim of this work is to study the prognostic impact of mutations in the myeloid transcription factor gene CEBPA (for CCAAT/enhancer binding protein-α) and expression of the BAALC gene (for brain and acute leukemia, cytoplasmic), a novel gene involved in leukemia, in 38 adults with AML and normal cytogenetics. Method: Screening for mutations of CEBPA gene was assessed using PCR-single-strand conformation polymorphism (PCR-SSCP), and BAALC expression was determined by real-time reverse transcriptase polymerase chain reaction in blood or bone marrow samples. Result: CEBPA mutations were found in 7 (18.4%) of 38 patients, 36.8 % (14 of 38) had low BAALC expression and 63.2 % (24 of 38) had high BAALC expression. Patients with CEBPA mutations had favorable course of their disease. They had higher rate of complete remission (CR) (85.7 % vs 51.6 %; p= 0.108), lower incidence of relapse (0% vs 41.9%; p= 0.038). Disease free survival (DFS) and overall survival (OS) were significantly longer for patients with CEBPA mutations compared with patients without mutations (mean 13.65±5.41 vs 7.32±4.33 months, p= 0.047; mean 15.32±6.5 vs 8.5±3.21 months, p= 0.039; respectively). Compared to low BAALC expressers, high BAALC expressers had lower incidence of CR (50% vs 71.4%; p= 0.171), higher incidence of relapse (50% vs 14.3%; p= 0.029), and showed significantly shorter DFS (mean 7.5±2.12 vs 11.67±4.6 months, p= 0.038) and inferior overall survival (mean 9.1±3.52 vs 13.22±4.21 months, p= 0.024). Conclusion: From this study, we can conclude that CEBPA mutation status and BAALC expression are important prognostic factors in AML patients with normal cytogenetics and their incorporation into novel risk-adapted therapeutic strategies will improve the currently disappointing cure rate of this group of patients.

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