m⁶A RNA methylation regulators predict prognosis and indicate characteristics of tumour microenvironment infiltration in acute myeloid leukaemia

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 <i>METTL14, YTHDC2, ZC3H13</i> and <i>RBM15</i> 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.