Patients with acute myeloid leukaemia (AML) have poor prognoses and low overall survival (OS) rates owing to its heterogeneity and the complexity of its tumour microenvironment (TME). N6-methyladenosine (m 6 A) modification plays a key role in the initiation and progression of haematopoietic malignancies. However, the underlying function of m 6 A regulators in AML remains elusive. This study thoroughly analysed the m 6 A modification features of 177 AML patients based on 22 m 6 A regulators. Utilizing unsupervised clustering, we determined three distinct m 6 A modification patterns related to different biological functions, TME cell-infiltrating characteristics and clinical outcomes. Additionally, a risk score was constructed based on six m 6 A regulators-associated prognostic signatures and was validated as an independent and valuable prognostic factor for AML. Patients with a low-risk score exhibited better survival than those with a high-risk score. Many m 6 A regulators were aberrantly expressed in AML, among which METTL14, YTHDC2, ZC3H13 and RBM15 were observed to be associated with the OS of AML. In addition, these four m 6 A regulators were found to be noticeably related to the immune checkpoint inhibitor (ICI) treatments. Finally, we verified the expression levels of these four m 6 A regulators in AML and healthy samples and three groups of AML patients with different risk categories. Collectively, our study indicates that the m 6 A modification pattern is involved in TME immune-infiltrating characteristics and prognosis in AML. A better understanding of the m 6 A modification pattern will help enhance our knowledge of the molecular mechanisms of AML and develop potential prognosis prediction indicators and more effective immunotherapeutic strategies.
Background: Patients with acute myeloid leukemia (AML) have a poor prognosis and low overall survival (OS) rate owing to its heterogeneity and the complexity of its tumor microenvironment (TME). N6-methyladenosine (m6A) modification plays a potential role in the initiation and progression of haematopoietic malignancies. Nonetheless, compressive analysis of RNA m6A modification is rare in AML.Methods: Based on somatic mutation and copy number analysis, differential expression analysis, survival analysis, function enrichment analysis, spearman correlation analysis, gene set enrichment analyses,and a series of experiments (western blot, quantitative reverse transcription polymerase chain reaction and flow cytometry), data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database were used to assess the value of m6A regulators in the development and prognosis of AML.Results: Compared with normal samples, five m6A regulators were significantly differentially expressed in AML samples. Among them, methyltransferase-like 14 (METTL14), zinc finger CCCH-type containing 13 (ZC3H13), RNA binding motif protein 15 (RBM15) and YTH domain-containing 2 (YTHDC2) were associated with the OS of AML patients. Notably, they were successfully validated in clinical samples. Besides, three distinct m6A modification patterns were determined, and remarkable differences were observed in the expression of m6A regulators, TME infiltration characterization, functional enrichment and survival outcome among these patterns. We further found 122 m6A phenotype-related differentially expressed genes (DEGs). Functional enrichment analysis revealed that the DEGs were closely relevant to metabolism. Based on 28 prognosis-related DEGs, m6Ascore system was established to evaluate patient prognosis, patients with high m6Ascore had higher survival rates than those with low m6Ascore. Importantly, m6Ascore may serve as a potential predictor independent of TMB. Conclusion: This work provided new insight into the potential functions of m6A regulators in the initiation and progression of AML. It indicated that some m6A regulators may serve novel biomarkers to predict the prognosis of AML.
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