microRNA 128a and 182 Profiles for Diagnosis and Prediction of Relapse in Pediatric Acute Lymphoblastic Leukemia-L1

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Abstract Acute lymphoblastic leukemia (ALL) represents the most prevalent form of cancer among children, accounting for nearly 75% of pediatric leukemia cases. Although therapeutic outcomes have improved, relapse still occurs in roughly 20 to 30% of patients, and the precise mechanisms underlying this remain uncertain. MicroRNAs (miRNAs) function as pivotal regulators at the post-transcriptional level, playing a significant role in leukemogenesis, and they hold promise as both diagnostic and prognostic indicators in childhood ALL. This research sought to examine the expression profiles of miR-128a and miR-182 to evaluate their usefulness as diagnostic markers and their potential role in predicting relapse among pediatric ALL patients. A cross-sectional investigation was conducted between November 2022 and October 2023 using serum samples from pediatric ALL patients before chemotherapy at Wahidin Sudirohusodo Hospital. A total of four groups were established for comparison: standard risk (SR), high risk (HR), RS, and healthy control (HC). Expression of miR-128a and miR-182 was measured through quantitative real-time PCR, with miR-103a-3p as the normalization control. Analytical procedures included ANOVA, Tukey's post-hoc test, and receiver operating characteristic (ROC) analysis. Expression levels of miR-128a and miR-182 differed significantly among SR, HR, RS, and HC groups (p < 0.001). miR-128a expression was markedly upregulated in HR compared with HC (388-fold, p = 0.0005) and SR (131-fold, p = 0.0024), while HC showed lower levels than RS (p = 0.017). miR-182 was also significantly upregulated in HR, RS, and SR compared with HC (p <0.001). ROC analysis demonstrated that miR-128a discriminated HR versus HC (area under the curve [AUC] 0.942) and HR versus SR (AUC 0.851), while miR-182 showed perfect discrimination (AUC 1.0) between HR versus HC and RS versus HC, with sensitivity and specificity >0.7. miR-128a expression was significantly higher in HR compared with SR and HC, indicating its potential as a diagnostic biomarker for high-risk (HR) ALL. miR-182 was upregulated in HR and RS groups relative to HC and demonstrated strong discriminatory power for relapse prediction. These findings suggest that miR-128a and miR-182 may serve as promising biomarkers for risk classification and relapse monitoring in pediatric ALL.

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