A mini-review: the role of glycosylation in acute myeloid leukemia and its potential for treatment

Abstract Glycosylation, a prevalent post-translational modification, involves the enzymatic addition of sugar moieties to specific amino acid residues in proteins. Aberrant glycosylation – stemming from dysregulated glycan-related gene expression – is increasingly recognized as a hallmark of cancer, including hematologic malignancies such as acute myeloid leukemia (AML). This study discusses: (1) glycosylation patterns in AML as biomarkers – AML and related myeloid disorders display specific alterations including enhanced sialylation, fucosylation, O-GlcNAcylation, and truncated O-glycans. These modifications influence cell adhesion, signaling, and disease subtypes, offering diagnostic and prognostic value, (2) therapeutic strategies targeting glycosylation pathways, including receptor glycosylation: approaches include inhibitors of glycosyltransferases, mevalonate-pathway blockers (e.g., statins), glycomimetic compounds, and combination regimens with TKIs or immunotherapies. Early-phase clinical trials support feasibility, and (3) the impact of altered glycosylation on immunosurveillance: abnormal glycan structures interact with lectins (e.g., galectins and siglecs), impairing T and NK cell function and promoting immune escape. Together, these insights support the rationale for developing glycosylation-focused therapeutic approaches to improve AML treatment outcomes.