Integrated analysis of single-cell RNA-seq and bulk RNA-seq reveals RNA N6-methyladenosine modification associated with prognosis and drug resistance in acute myeloid leukemia

Acute myeloid leukemia (AML) is a type of blood cancer that is identified by the unrestricted growth of immature myeloid cells within the bone marrow. Despite therapeutic advances, AML prognosis remains highly variable, and there is a lack of biomarkers for customizing treatment. RNA N6-methyladenosine (m A) modification is a reversible and dynamic process that plays a critical role in cancer progression and drug resistance. To investigate the m A modification patterns in AML and their potential clinical significance, we used the AUCell method to describe the m A modification activity of cells in AML patients based on 23 m A modification enzymes and further integrated with bulk RNA-seq data. We found that m A modification was more effective in leukemic cells than in immune cells and induced significant changes in gene expression in leukemic cells rather than immune cells. Furthermore, network analysis revealed a correlation between transcription factor activation and the m A modification status in leukemia cells, while active m A-modified immune cells exhibited a higher interaction density in their gene regulatory networks. Hierarchical clustering based on m A-related genes identified three distinct AML subtypes. The immune dysregulation subtype, characterized by mutation and copy number variation, was associated with a worse prognosis and exhibited a specific gene expression pattern with high expression level of and , and low expression level of and . Notably, patients with the immune dysregulation subtype were sensitive to immunotherapy and chemotherapy. Collectively, our findings suggest that m A modification could be a potential therapeutic target for AML, and the identified subtypes could guide personalized therapy.