A 2025 BMC Cancer study identified ASAH1 and altered sphingolipid metabolism as drivers of venetoclax resistance in acute myeloid leukemia (AML), particularly in monocytic phenotypes. The research maps how sphingolipid pathway remodeling undermines BCL‑2 inhibitor efficacy and points to metabolic enzymes as potential co‑targets to restore sensitivity. The findings offer a mechanistic basis for combining venetoclax with agents that modulate sphingolipid metabolism or target ASAH1, and provide biomarkers to stratify patients at risk for early resistance. Translational teams may use these data to design combination trials and companion diagnostics.