Decoding the AML1/ETO translocation cipher: In-depth exploration into the pathogenesis and cutting-edge therapeutic strategies of t(8;21) acute myeloid leukemia.

The t(8;21) acute myeloid leukemia (AML) is driven by the AML1-ETO (AE) fusion protein formed through the translocation of chromosomes 8 and 21, which mediates AML malignant transformation via epigenetic reprogramming and cooperative genetic events. This review comprehensively delineates the molecular pathogenesis of the disease, emphasizing that splice isoforms such as AE9a acquire enhanced leukemogenic potential due to the loss of critical structural domains. Emerging evidence demonstrates that epigenetic dysregulation-including aberrant DNA methylation, dysregulated histone modifications, and non-coding RNA-mediated regulatory networks-synergizes with AE to orchestrate leukemogenesis. Furthermore, dysregulated signaling pathways and concurrent genetic alterations critically contribute to the pathogenesis of t(8;21) AML. In terms of therapeutic strategies, conventional epigenetic drugs such as histone deacetylase (HDAC) inhibitors still exhibit limited clinical efficacy, while novel therapies targeting the pathogenic domains of AE, modulating dynamic miRNA regulatory networks, and suppressing key oncogenic pathways like c-Myc demonstrate promising potential. Furthermore, plant-derived natural products, leveraging their multi-target effects and low-toxicity profiles in conjunction with the precision modulation capabilities of nanoparticle delivery systems, provide groundbreaking avenues to overcome therapeutic resistance and relapse.