Researchers at the University of Colorado Anschutz Cancer Center have found that stem cells driving high-risk myelodysplastic syndromes (MDS) rely unusually heavily on the energy molecule NAD. The study, published in Blood Cancer Discovery, describes this dependence as an "energy addiction" that distinguishes the cancer stem cells from healthy blood-forming cells.
MDS is a group of blood cancers that impair the bone marrow's ability to produce healthy blood cells, often leading to severe anemia, infections, and a risk of progressing to acute myeloid leukemia. The researchers compared MDS stem cells with normal stem cells and found that the cancer cells use NAD at a much higher rate and depend on a recycling pathway involving the enzyme NAMPT to maintain their supply.
When the researchers blocked NAMPT in patient-derived cells and animal models, NAD levels dropped and the MDS stem cells entered an energy crisis, while healthy stem cells were better able to compensate. This selective vulnerability could allow future drugs to weaken the disease-driving cells without harming normal blood production.
The team now plans to investigate NAMPT-targeting drugs in clinical studies for MDS and related blood cancers. Because this report is based on a single source, there are no differing perspectives to compare, but the findings offer a concrete metabolic difference that may be exploitable for more precise treatments. The study was co-led by Eric M. Pietras and Craig T. Jordan, with laboratory work led by Sweta B. Patel.