Cuproptosis in acute myeloid leukemia from heme biosynthesis inhibition

Heme plays a diverse role in enzymatic and signaling functions.

The researchers observed reduced levels of the essential metabolite heme are a common feature of acute myeloid leukemia, and consequently, leukemic cells are highly sensitive to inhibition of de novo heme synthesis.

The authors show that leukemic stem cells (LSCs) downregulate heme biosynthesis enzymes (HBEs), which promotes their self-renewal.

Blockade of heme biosynthesis enzymes triggers cuproptosis due to collapse of mitochondrial Complex IV and dysregulation of copper-chaperone system.

https://www.cell.com/cell/fulltext/S0092-8674(25)01233-4

https://sciencemission.com/heme-biosynthesis-triggers-cuproptosis