Evaluation of FOXP3 Gene Expression Level in Childhood Acute Lymphoblastic Leukemia

Abstract

Background: Despite the favorable survival rates of childhood B-cell acute lymphoblastic leukemia (B-ALL), a significant number of patients present a dismal prognosis. Forkhead box P3 (FOXP3), a marker of regulatory T cells, functions as a transcription factor involved in immune cell regulation and its expression correlates with prognosis in many malignancies. Therefore, this study aimed to assess the relative expression level of FOXP3 in childhood B-ALL and to detect its prognostic utility. Methods: The study included 139 bone marrow samples obtained from 112 patients at diagnosis and 27 healthy children. Following extraction, RNA was reverse transcribed and the relative expression level of FOXP3 was quantified by quantitative PCR. Cytogenetics, immunophenotype, and minimal residual disease were analyzed according to international guidelines. Results: A highly significant over-expression of FOXP3 was detected in childhood B-ALL patients at diagnosis which was associated with a stronger risk for disease relapse and patients’ worse survival. Moreover, multivariate regression models highlighted the independent prognostic value of FOXP3 for childhood B-ALL. Finally, the combination of FOXP3 relative expression with clinically used disease markers clearly enhanced the prediction of treatment stratification. Conclusions: High FOXP3 relative expression was associated with inferior outcome suggesting its potentiality as a molecular prognostic marker to predict childhood B-ALL patients’ outcomes.