Enzyme inhibition curbed mutant blood cell expansion in zebrafish
Experiments in zebrafish targeted an enzyme involved in processing choline, a nutrient, and reduced expansion of blood-forming cells carrying a mutation.
Limit: Mutant-cell expansion is a surrogate for blood cancer, cardiovascular disease, and survival outcomes
Edited by Boris Djordjevic · AgingResearch.News
In zebrafish experiments, researchers tracked blood-forming stem and precursor cells to study clonal hematopoiesis, the expansion of groups of blood cells with shared mutations. Cells with a mutation in the asxl1 gene showed altered processing of choline, a nutrient. They also made more phosphatidylcholine, a membrane fat. Suppressing choline processing through the enzyme choline kinase alpha reduced mutant-cell expansion.
The effect also occurred in a mouse model involving the DNMT3A gene and a human model involving the TET2 gene. The pathway supported production of platelet-activating factor, a signaling molecule. In blood-forming cells taken from people with ASXL1 mutations and tested outside the body, disrupting this signaling reduced the mutant cells’ ability to compete with other cells.
Why it matters
Clonal hematopoiesis affects aging populations and is associated with increased risks of blood cancers, cardiovascular disease and death. Understanding its metabolic requirements could help guide research into treatments, which remain limited.
Caveats
These were model experiments and tests on human cells outside the body, not a treatment study in people. The findings come from a preprint that has not been peer-reviewed.
The paper
Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA, Howard Hughes Medical Institute
bioRxiv, Oct 28, 2026, Open access, Preprint, not peer-reviewed
