Work

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

Year: 2025

Type: article

Abstract: 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.

Source: PeerJ

DOI: 10.7717/peerj.20371