A microRNA signature for clinical outcomes of pediatric ALL patients treated with TPOG protocols.

MicroRNA (miRNA) expression is reportedly associated with clinical outcomes in childhood acute lymphoblastic leukemia (ALL). Here, we aimed at investigating whether miRNA expression is associated with clinical outcomes in pediatric ALL patients treated with the Taiwan Pediatric Oncology Group (TPOG) protocols. The expression of 397 miRNAs was measured using stem-loop quantitative real-time polymerase chain reaction miRNA arrays in 60 pediatric ALL patients treated with TPOG-ALL-93 or TPOG-ALL-97 VHR (very high-risk) protocols. In order to identify prognosis-related miRNAs, original cohort was randomly split into the training and testing cohort in a 2:1 ratio, and univariate Cox proportional hazards regression was applied to identify associations between event-free survival (EFS) and expressions of miRNAs. Four prognosis-related miRNAs were selected and validated in another independent cohort composed of 103 patients treated with the TPOG-ALL-2002 protocol. Risk score, including the impact of four prognosis-related miRNAs, was calculated for each patients, followed by grouping patients into the high or low risk-score groups. Irrespective of the training, testing, or validation cohort, risk-score group was significantly associated with EFS and overall survival (OS). Risk-score group combining with clinical characteristics including the age onset (≥10 years), white blood cell counts (≥100 × 10/L), cell type (T- or B-cell), sex, and risk groups of the treatment protocols were used as predictors of EFS using the multivariate Cox proportional hazards regression. Results showed that the risk-score group was the strongest predictor. In the validation cohort, hazard ratios (HRs) of the risk-score group were 7.06 (95% CI=1.93-25.84, -value =0.003) and 14.03 (95% CI=3.34-59.04, -value =0.003) for EFS and OS, respectively. High risk-score group had higher risk of having poor prognosis and risk of death than that in the low risk group. Accuracy of the prediction model for 5-year EFS could reach 0.76. For the prediction of 5-year OS, accuracy was 0.75. In conclusion, a miRNA signature was associated with clinical outcomes in childhood ALL patients treated with TPOG protocols and might be a suitable prognostic biomarker.