Mechanisms and clinical implications of microRNA associations and signaling pathways in B-cell acute lymphoblastic leukemia.

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.