Background: Acute lymphoblastic leukemia (ALL), the most common childhood cancer with a peak incidence in children from 2-5 years old, might be associated with poor prognosis and resistance to therapy in specific cytogenetic backgrounds. FoxO3a, a member of the forkhead class ‘O’ (FoxO) transcription factors, is a main downstream target of PI3K/AKT pathway which regulates different variety of biological processes and is overactivated in several human cancers. We aimed to evaluate the aberration of the FoxO3a gene in mRNA level in childhood ALL and compare them with healthy controls. 
Methods: Real-time quantitative RT-PCR (qRT-PCR) was used to detect FOXO3a expression in 30 new cases of pediatric ALL and 30 age- and sex-matched healthy children as the control group. 
Results: the expression level of the FoxO3a gene was significantly lower in ALL patients compared to healthy controls (P<0.0001), while no difference was observed between the two sub-types B- and T-ALL. 
Conclusion: Our study suggested that decreased FoxO3a expression may play an important role in the development of pediatric ALL. FoxO3a could be considered as a molecular target of therapy in ALL malignancy.