MiR-181a in Pediatric Acute Lymphoblastic Leukemia of the Central Nervous System

Understanding the molecular biology of pediatric central nervous system (CNS) acute lymphoblastic leukemia (ALL) is crucial for developing new CNS-directed therapies. Recently, we identified vascular endothelial growth factor A (VEGF) as a regulator for CNS ALL aiding ALL transmigration into and adaptation to the nutrient-low CNS niche. In cerebrospinal fluid of patients miR-181a was reported to be a biomarker for CNS ALL and to regulate VEGF expression in chondrosarcoma. Hence, we evaluated the association of miR-181a and VEGF in CNS ALL. We analyzed VEGF and miR-181a expression in 22 patient-derived xenograft samples. VEGF was significantly upregulated in CNS- compared to bone marrow-derived ALL cells. Despite no differential expression of miR-181a, a significant correlation with VEGF expression was found. MiR-181a mimics had no effect on transmigration, yet VEGF protein increased significantly exclusively in low-nutrient conditions. In sum, miR-181a regulates VEGF expression in ALL cells cultured in conditions mimicking the CNS milieu. MiR-181a target genes interposed to VEGF require identification with the possibility to establish novel CNS-directed druggabilities.

Publication History

Article published online:
10 May 2024