Glycolysis and glycolytic enzymes in acute myeloid leukemia: Warburg and beyond.

The ability to generate and regulate energy, maintain metabolic flux, and preserve redox homeostasis is the basis of all cellular processes in both healthy and diseased tissues. While the importance of glycolytic metabolism in cancer biology is well established, the clinical translation of metabolic targeting strategies remains limited. A deeper understanding of how energy flux is regulated and how metabolic enzymes contribute to cell survival, proliferation, differentiation, and therapy response will help identify cancer-specific metabolic dependencies and drive novel therapeutic approaches. Recent advances in molecular and metabolic profiling have highlighted the multifaceted roles of glycolytic enzymes beyond their canonical functions. In this review, we summarize current knowledge on glycolytic enzymes and their involvement in normal and malignant myelopoiesis, with a particular focus on acute myeloid leukemia (AML). AML cells exhibit high glycolytic activity and frequently overexpress key glycolytic enzymes. Beyond their metabolic functions, these enzymes also exert regulatory roles in signaling, transcriptional control, and redox balance. Here, we discuss both the canonical and non-canonical functions of glycolytic enzymes and evaluate their potential as therapeutic targets in AML.