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 (m⁶A) modification plays a key role in the initiation and progression of haematopoietic malignancies. However, the underlying function of m⁶A regulators in AML remains elusive. This study thoroughly analysed the m⁶A modification features of 177 AML patients based on 22 m⁶A regulators. Utilizing unsupervised clustering, we determined three distinct m⁶A modification patterns related to different biological functions, TME cell-infiltrating characteristics and clinical outcomes. Additionally, a risk score was constructed based on six m⁶A 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 m⁶A 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 m⁶A regulators were found to be noticeably related to the immune checkpoint inhibitor (ICI) treatments. Finally, we verified the expression levels of these four m⁶A regulators in AML and healthy samples and three groups of AML patients with different risk categories. Collectively, our study indicates that the m⁶A modification pattern is involved in TME immune-infiltrating characteristics and prognosis in AML. A better understanding of the m⁶A modification pattern will help enhance our knowledge of the molecular mechanisms of AML and develop potential prognosis prediction indicators and more effective immunotherapeutic strategies.

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