Can we selectively target AML stem cells?

De novo acute myeloid leukemia (AML) leukemia stem cell (LSC) populations are uniquely dependent on amino acid metabolism to drive the TCA cycle and oxidative phosphorylation. Oxidative phosphorylation can be selectively downregulated in de novo AML LSC populations by perturbing amino acid metabolism via BCL2 inhibition with venetoclax. While venetoclax-based therapies have shown high response rates, not all patients achieve remission. It may be possible to prospectively identify the patients who will most likely respond to venetoclax-based treatment by analyzing the metabolic properties of individual patients. Specifically, it appears that patients who are likely to be resistant to venetoclax-based therapy are able to employ alternate metabolic pathways to drive oxidative phosphorylation.