A BMC Cancer study identified ASAH1 and its impact on sphingolipid metabolism as a key mediator of resistance to venetoclax in acute myeloid leukemia, especially in monocytic phenotypes. The authors mapped metabolic shifts that blunt venetoclax efficacy and suggested targeting sphingolipid pathways to resensitize resistant cells. Findings highlight metabolic rewiring as a drug-resistance mechanism and point to candidate combination strategies for clinical testing.