The Non-Coding Code: Silent Regulators of MEG3 and Let-7i-3p/5p in the Progression of Acute Lymphoblastic Leukemia

OBJECTIVE: Acute lymphoblastic leukemia (ALL) is one of the most common malignancies worldwide. The long non-coding RNA MEG3 functions as a tumor suppressor in several cancers, potentially influencing gene expression through transcriptional, translational, and epigenetic mechanisms. let-7i plays a role in leukemia progression. This study aimed to evaluate MEG3 gene expression in adult ALL patients and investigate its possible regulatory interaction with let-7i-3p and let-7i-5p. METHODS: A total of 83 blood samples, classified in a case-control study design, were collected from newly diagnosed ALL patients (n=53) and healthy controls (n=30). Hematological parameters were estimated using a CBC analyzer. RNA was extracted and reverse-transcribed into cDNA. Quantitative real-time PCR with gene-specific primers was employed to assess MEG3 and let-7i-3p/5p expression levels. RESULTS: ALL patients and healthy controls were matched for age (29.0±9.9 vs. 28.6±7.7 years, p=0.862) and sex (p=0.299). Hematological analysis revealed significant cytopenias in patients, including reduced Hemoglobin (Hb) (8.60±1.75 vs. 14.72±2.51 g/dL; p<0.001), white blood cells (WBCs) (4.91±2.84 vs. 7.96±1.57×109/L; p<0.001), and platelets (PLT) (156.96 ± 35.64 vs. 269.93±55.35×109/L; p<0.001). Gene expression analysis revealed that MEG3 was significantly downregulated in ALL patients (fold change 0.535±0.273; p=0.001), whereas Let-7i-3p/5p were upregulated (fold changes 1.875 ± 0.732 and 1.857 ± 0.891: p=0.003 and 0.004, respectively), indicating a different dysregulation pattern associated with adult ALL. CONCLUSION: This study demonstrates that adult ALL patients exhibit hematological abnormalities including anemia, leukopenia, and thrombocytopenia. Molecular analysis revealed a significant downregulation of lncRNA MEG3, alongside upregulation of let-7i-3p/5p, suggesting their potential involvement in leukemogenesis. These findings highlight the diagnostic and possibly prognostic relevance of MEG3 and let-7i in adult ALL and provide a basis for further investigation into their mechanistic roles and therapeutic targeting.