Mechanisms and clinical implications of microRNA associations and signaling pathways in B-cell acute lymphoblastic leukemia.
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PURPOSE: This comprehensive review examines the clinical significance of microRNA (miRNA) dysregulation in B-cell acute lymphoblastic leukemia (B-ALL), bridging the gap between mechanistic understanding and clinical translation by exploring validated biomarker applications and addressing therapeutic implementation challenges in pediatric and adult populations. METHODS: A comprehensive literature review was conducted to assess the role of miRNA in B-ALL pathogenesis, treatment response, and clinical outcomes. Clinical and experimental findings were examined to understand the therapeutic implications of targeting miRNA pathways. RESULTS: Specific miRNA profiles differentiate B-ALL from other leukemia subtypes, predicting treatment outcomes and relapse risk with clinical significance. Significant dysregulation of key miRNAs, especially miR-155, miR-150, and members of the let-7 family, seems to influence the PI3K/AKT, JAK/STAT, NOTCH, and Wnt signaling pathways. An 8-miRNA signature achieved 78 % accuracy in predicting prednisone response in 650 pediatric patients, leading to adjustments in treatment protocols. miR-124a methylation testing showed improved 3-year event-free survival in clinical practice. miR-181a/TGF-β1 biomarkers were validated across 15 countries and integrated into international protocols. However, therapeutic applications face notable barriers, including delivery efficiency, safety concerns, and resistance mechanisms that hinder widespread implementation. CONCLUSIONS: Current evidence supports the use of miRNAs as validated biomarkers for B-ALL, demonstrating a significant impact on risk stratification and personalized treatment care. Ongoing research into improved delivery systems and comprehensive safety assessments is essential for unlocking the full therapeutic potential of miRNA-based treatments for B-ALL.