The commentary “Alpha-enolase promotes progression of acute myeloid leukemia via MAPK/ERK signaling pathway” by Zhang et al., published in Blood Science (2025), examines the clinical and biological significance of ENO1 in acute myeloid leukemia (AML). ENO1, a glycolytic enzyme with additional regulatory roles, has been implicated in several solid tumors, but its function in AML had not been fully clarified. Through integrated analyses of patient samples, functional assays, transcriptomics, and in vivo models, the authors demonstrate that ENO1 is overexpressed in AML and promotes disease progression mainly through MAPK/ERK pathway activation.