Background Acute myeloid leukemia (AML) is a highly heterogeneous malignant hematological tumor, and its occurrence and development are closely related to immune evasion. Programmed death ligand 1 (PD-L1) is a key molecule mediating tumor immune escape, but its regulatory mechanism in AML has not been fully elucidated. The m6A demethylase ALKBH5 is highly expressed in various cancers, including AML, and promotes disease progression, but its specific role in modulating the PD-L1 axis and the immune microenvironment in AML remains unclear. Methods We analyzed the expression and prognostic significance of ALKBH5 in AML by integrating BloodSpot, GEO, and TCGA databases, and performed functional enrichment and immune infiltration analyses. Bone marrow samples from 77 newly diagnosed AML patients and 13 healthy controls were collected for RT-qPCR validation, and their correlations with clinical features and PD-L1 expression were evaluated. ALKBH5 stable knockdown AML cell lines (THP-1 and MOLM-13) were constructed to assess cell proliferation, migration, and PD-L1 expression. T cell anti-tumor effects were evaluated using an AML cell and activated PBMC co-culture system. Results Bioinformatics analysis shows that ALKBH5 is significantly overexpressed in AML and is associated with poor prognosis and enrichment of immune related signaling pathways. Clinical sample testing further confirms that the level of ALKBH5 in AML patients is elevated, which is positively correlated with an increase in the proportion of primitive cells and PD-L1 expression. In vitro experiments have shown that ALKBH5 knockdown significantly inhibits AML cell proliferation and migration, while reducing PD-L1 protein levels without affecting its mRNA expression, suggesting that it regulates PD-L1 through post transcriptional mechanisms. Co-culture experiments showed that ALKBH5 knockdown enhanced the proportion of CD8 + T cells and secretion of IFN-γ/TNF-α, and reduced the survival rate of AML cells. Conclusions ALKBH5 may promote AML progression and immune escape through the upregulation of PD-L1 and modulation of T-cell function, which provides a theoretical basis for the development and screening of novel immunotherapeutic strategies for AML.
Ma et al. (Thu,) studied this question.