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Objectives To study E2F3a expression and its clinical significance in children with acute lymphoblastic leukemia ( ALL). Methods We quantified E2F3a expression at diagnosis in 148 children with ALL by real-time PCR. In the test cohort ( n = 48), receiver operating characteristic ( ROC) curve was used to find the best cut-off point to divide the patients into E2F3a low- and high-expression groups. The prognostic significance of E2F3a expression was investigated in the test cohort and confirmed in the validation cohort ( n = 100). The correlations of E2F3a expression with the clinical features and treatment outcome of these patients were analyzed. Results ROC curve analysis indicated that the best cut-off point of E2F3a expression was 0.3780. In the test cohort, leukemia-free survival ( LFS) and event-free survival ( EFS) of the low-expression group were lower than those of the high-expression group (log rank: P = 0.026 for both). This finding was verified in the validation cohort. LFS, EFS, and overall survival were also lower in the low-expression group than in the high-expression group (log rank, P = 0.015, 0.008, and 0.002 respectively). E2F3a low expression was correlated with the existence of BCR- ABL fusion. An algorithm composed of E2F3a expression and minimal residual disease ( MRD) could predict relapse or induction failure more precisely than current risk stratification. These results were still significant in the ALL patients without BCR- ABL fusion. Conclusions Low expression of E2F3a was associated with inferior prognosis in childhood ALL. An algorithm composed of E2F3a expression and MRD could predict relapse or induction failure more precisely than that of the current risk stratification. [ABSTRACT FROM AUTHOR]