Discover oncology · 2026
Genome-wide investigation of differentially expressed alternative splicing and RNA-binding protein genes association with AML drug resistance.
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Zhang Yu-Mei, Dong Xue-Yan, Zheng Wei, Xu Jie, Wang Zhen-Zhen, Ding Shu-Min, Wang Ying-Ying, Wang Jing-Yi
Аннотация
BACKGROUND: Acute myeloid leukemia (AML) is a hematologic malignancy with persistently poor outcomes. Despite advances in chemotherapy, targeted therapy, and hematopoietic stem cell transplantation, drug resistance and relapse remain major obstacles, with the global 5-year survival rate for adults with AML below 50%. The molecular mechanisms underlying relapse and drug resistance are not fully understood.
METHODS: Bone marrow mononuclear cells were isolated from four patients with AML relapse (reAML), three patients with AML remission, and five healthy donors. RNA sequencing was performed, followed by differentially expressed genes (DEGs) analysis, overlapping analysis, weighted gene co-expression network analysis (WGCNA) and co-expression analysis, alternative splicing (AS) analysis and functional enrichment analysis.
RESULTS: We identified 593 upregulated and 999 downregulated genes specifically in reAML group compared with both AML remission and healthy groups. Notably, 33 RNA-binding protein (RBP) genes were consistently up-regulated and 30 down-regulated in reAML group. WGCNA and AS analyses revealed marked splicing alterations in reAML group, accompanied by multiple differential regulatory alternative splicing genes (RASGs) and events (RASEs).
CONCLUSIONS: This study provides a systematic landscape of RBP dysregulation and aberrant alternative splicing in AML relapse and drug resistance. These findings highlight RBPs and alternative splicing events (ASEs) as potential clinical biomarkers and therapeutic targets. Our work opens new avenues for predicting relapse risk and overcoming drug resistance in AML patients.
METHODS: Bone marrow mononuclear cells were isolated from four patients with AML relapse (reAML), three patients with AML remission, and five healthy donors. RNA sequencing was performed, followed by differentially expressed genes (DEGs) analysis, overlapping analysis, weighted gene co-expression network analysis (WGCNA) and co-expression analysis, alternative splicing (AS) analysis and functional enrichment analysis.
RESULTS: We identified 593 upregulated and 999 downregulated genes specifically in reAML group compared with both AML remission and healthy groups. Notably, 33 RNA-binding protein (RBP) genes were consistently up-regulated and 30 down-regulated in reAML group. WGCNA and AS analyses revealed marked splicing alterations in reAML group, accompanied by multiple differential regulatory alternative splicing genes (RASGs) and events (RASEs).
CONCLUSIONS: This study provides a systematic landscape of RBP dysregulation and aberrant alternative splicing in AML relapse and drug resistance. These findings highlight RBPs and alternative splicing events (ASEs) as potential clinical biomarkers and therapeutic targets. Our work opens new avenues for predicting relapse risk and overcoming drug resistance in AML patients.