Exosome and BCR-ABL mediated molecular alterations in endothelial cells in chronic myeloid leukemia: identification of seven genes and their regulatory network.

BACKGROUND: Chronic myeloid leukemia (CML) progression relies on dynamic crosstalk between leukemic cells and vascular niches. Here, we investigate how exosomes and BCR/ABL overexpression influence endothelial functions, aiming to identify key mediators of leukemia-induced microenvironmental remodeling as potential therapeutic targets. METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured and divided into four groups: control (Z), treated with K562-derived exosomes (Zexo), BCR-ABL-overexpressing (ZBA), and BCR-ABL-overexpressing with exosome treatment (ZBAexo). Transcriptomic profiling was performed to identify DEGs, followed by functional enrichment and protein-protein interaction network analyses. Gene Set Enrichment Analysis (GSEA) was applied to uncover associated biological pathways. RESULTS: Seven specificized expressed genes in ZBAexo group were identified: CAMK2B, CDC25C, SV2A, MND1, CDC20, CLSPN, and GRM1. These genes are involved in cell cycle, DNA replication, and cell adhesion pathways and show significant correlation with the BCR/ABL fusion gene. Expression of these genes was strongly associated with BCR-ABL. Network analysis revealed the potential regulatory roles of transcription factors CREB1 and NFKB1. A competing endogenous RNA (ceRNA) network involving miRNAs (e.g., miR-16-5p, miR-126-5p) and lncRNAs (e.g., AC008124.1, AC064799.2, AGAP11) potentially modulates their expression. CONCLUSION: This study identifies seven novel candidate biomarkers dysregulated in endothelial cells under combined BCR-ABL and exosomal stimulation, shedding light on the molecular crosstalk between leukemic cells and the vascular niche.