Scientists thought they knew how this 70-year-old leukemia drug worked

A 70-year-old leukemia drug is still revealing new secrets. Researchers found that removing a protein called NUDT5 protected cells from the drug, even though simply blocking the protein had little effect. The unexpected result points to a hidden cellular role that could help explain why people respond differently to certain leukemia treatments.

Scientists thought they knew how this 70-year-old leukemia drug worked. Its effects in patients are well documented, but researchers are still working to understand the molecular details that determine why some cells are killed by the drug while others manage to withstand it. A team at the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, working with scientists at the University of Oxford, the Weizmann Institute of Science and the University of Dundee, has now identified an unexpected factor in that response: a protein called NUDT5.

The finding follows a recent discovery from the Kubicek and Huber laboratories ( Science, 2025). That earlier work showed that NUDT5 has an important role inside cells that does not depend on its usual enzymatic activity. Rather than functioning only as a catalyst that drives chemical reactions, NUDT5 can also act as a molecular scaffold that helps organize cellular metabolism.