〔Abstract〕 Objective To investigate the aberrant alterations of microRNAs(miRNAs) in exosomes derived from bone marrow stromal cells(BMSCs) in the bone marrow supernatants of patients with acute myeloid leukemia(AML) and their impact on the prognosis of AML patients.Methods Bone marrow supernatant samples were collected from three AML patients and three healthy donors.Exosomes were isolated using a commercial kit,identifying the morphology and marker expression,and subjected to miRNA sequencing to determine differentially expressed miRNAs(DE-miRNAs).The DE-miRNAs were then intersected with the exosomal miRNA expression profiles of primary AML cells(GSE64029) to exclude AML cell-derived signals and to identify BMSC-derived DEmiRNAs.Subsequently,candidate miRNAs were identified through Cox regression and Lasso regression analyses based on data from The Cancer Genome Atlas(TCGA).A prognostic risk model for AML was constructed,and patients were stratified into high-risk and low-risk groups according to the median risk score.The prognostic value and clinical relevance of the model were further validated.Finally,the target genes of the candidate miRNAs were predicted,followed by pathway enrichment analysis,construction of key regulatory networks,and correlation analysis between the expression levels of key miRNAs and their corresponding target genes.Results Isolated exosomes exhibited a typical cup-shaped morphology with intact structures with particle size of 30-150 nm,and expressed exosomal markers CD63,ALIX,and TSG101.miRNA sequencing identified 103 DE-miRNAs in AML patients compared with healthy donors;after intersection with the GSE64029 dataset,83 BMSC-derived DE-miRNAs were retained.Among these,five candidate miRNAs(miR-25-3p,miR-532-5p,miR-194-5p,miR-10a-5p,and miR-20a-5p) were used to construct the prognostic model.Kaplan-Meier survival analysis demonstrated significantly longer overall survival in the low-risk group compared with the high-risk group(P