High-risk myelodysplastic syndrome, a bone marrow cancer that can turn into acute myeloid leukemia, is driven by stem cells that burn through an unusually large supply of one molecule: nicotinamide adenine dinucleotide, or NAD. Researchers at the University of Colorado Anschutz Cancer Center, with Eric M. Pietras and Craig T. Jordan as co-lead authors, reported in Blood Cancer Discovery that these cells depend on NAD far more than healthy blood stem cells do, and that choking off the supply hurts the cancer cells first.
The result is a laboratory one. It comes from patient-derived marrow cells and animal models, not from a treatment given to people, and the university announced it in August 2026, well before the October reposts that carried it to a wider audience.
NAD and the energy addiction
NAD is a cofactor that cells use to move electrons through the reactions that make energy, so every cell needs it. The Colorado group’s point is about quantity. According to the University of Colorado Anschutz release, Pietras described cells that “had developed a much greater need for this resource,” using NAD “at a much higher rate than normal cells.” The team calls the pattern an energy addiction.
That language matters because addiction implies a weak point. A cell that has rebuilt its metabolism around one supply line cannot easily switch to another when the line is cut, and the preprint version of the work reports exactly that kind of inflexibility: high-risk cells consumed more oxygen than normal ones and relied on recycling NAD to keep going.
NAMPT, the recycling enzyme
Cells make NAD partly by recycling it, and the rate-limiting step in that salvage pathway is an enzyme called NAMPT, short for nicotinamide phosphoribosyltransferase. Sweta B. Patel directed the laboratory studies, with metabolomics collaborators Angelo D’Alessandro and Julie Reisz Haines, and the group aimed at NAMPT as the way to cut NAD off.
In the bioRxiv preprint that preceded the journal paper, the inhibitor was a compound called OT-82, tested on primary high-risk marrow specimens, on a cell line derived from a high-risk patient, on mice carrying human cells, and in CRISPR knockouts of the gene. Preprint numbers can shift before publication, but the preprint reported a threefold rise in cell death and a 50 percent drop in viable high-risk stem and progenitor cells, while healthy control cells were not significantly affected.
Selective weakening, not a treatment yet
The selectivity is the part that makes the finding interesting. The university’s account says blocking NAMPT weakened the cancer stem cells while normal blood-forming stem cells showed a better ability to compensate, which is the gap a drug would need in order to spare healthy marrow. eCancer’s report of the release quotes Pietras saying the cells relied on “a specific set of proteins and processes,” a dependence he described as a vulnerability that could potentially be targeted.
Nothing here shows that blocking NAMPT is safe or effective in people. The release says the next step is evaluating NAMPT-targeting drugs in clinical studies for MDS and related blood cancers, and the News-Medical summary lists support from the National Institutes of Health, the Edward P. Evans Foundation and Blood Cancer United.
The need is plain. As the National Cancer Institute’s patient guide describes it, MDS arises when immature blood cells in the marrow fail to mature, leaving too few healthy cells and a risk of infection, anemia and bleeding. Standard drug therapy includes azacitidine and decitabine, which can slow progression, and a stem cell transplant with chemotherapy offers a potential cure only for patients who are eligible for it.
NAMPT inhibitors in the clinic
Metabolic drugs have a long history of working in a dish and failing in the clinic, usually because the target is also needed by healthy tissue. NAD is needed everywhere, which is why the comparison with normal blood stem cells carries the whole argument. In the preprint data the healthy cells tolerated the inhibitor; whether that holds in patients, over months of dosing, and in marrow already weakened by disease is exactly what a trial would measure. Azacitidine and decitabine, the standard drugs named by the cancer institute, only slow progression, so a NAMPT inhibitor would have to show a measurable benefit beside them or after them, and the preclinical papers cannot supply that answer.
Pietras, an associate professor in the university’s hematology division, co-led the paper, and the release names clinical evaluation of NAMPT-targeting drugs as the next step. The published paper sits in volume 7, issue 5 of Blood Cancer Discovery, and its authors have put the clinical question in front of the field: whether a NAMPT inhibitor can be dosed so that high-risk MDS stem cells run out of NAD while the rest of the marrow keeps enough.
This article was produced with the assistance of AI and reviewed by Morning Overview editors prior to publication.
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