TET enzyme loss drives chromosomal instability and aggressive lymphoid growth
A preprint from Cold Spring Harbor Laboratory shows that loss of Tet2 and Tet3 in mouse immune cells consistently selects for trisomy 17, offering a mechanistic window into how epigenetic mutations may fuel blood cancers.
Researchers at Cold Spring Harbor Laboratory report in a bioRxiv preprint that deletion of the DNA dioxygenases Tet2 and Tet3 in invariant natural killer T (iNKT) cells drives aggressive lymphoid expansion consistently accompanied by trisomy of chromosome 17. The finding was reproduced across more than ten independently derived tumours following transplantation into immunocompromised host animals, suggesting that this specific aneuploid state confers a strong proliferative advantage rather than arising by chance.
TET2 loss-of-function mutations are among the most prevalent epigenetic alterations seen in clonal haematopoiesis and in myeloid and lymphoid malignancies in humans. This mouse study extends that picture by demonstrating that TET enzyme deficiency does not merely impair DNA demethylation but actively reshapes the genome through selection for specific chromosomal gains. The recurrent nature of the chromosome 17 trisomy implies that particular genes on that chromosome — candidates for which are discussed in the preprint — provide a selective growth advantage in cells already lacking TET-mediated epigenetic control.
Because TET2 mutations are common in clonal haematopoiesis of indeterminate potential (CHIP), a condition detectable in the general population with increasing age, understanding how TET loss interacts with genome stability pathways is of broad relevance to cancer biology and haematological research. The work is a preprint and has not yet completed peer review.
Plain-language version
For patients, families, and general readers. Educational only — not medical advice.
Researchers at Cold Spring Harbor Laboratory have published early findings — not yet peer reviewed — about how certain gene mutations affect blood cells in mice. The genes studied, called TET2 and TET3, help control how DNA is chemically marked inside cells. When both genes were switched off, immune cells in mice multiplied aggressively and consistently gained an extra copy of one chromosome. Similar TET2 mutations are known to occur in human blood cells as people age, and are sometimes linked to an increased risk of blood cancers. This mouse study helps scientists understand one way those mutations might cause problems. The research does not involve human patients and is at an early, laboratory stage. This is an educational summary, not medical advice. If anything here raises questions for you, please speak with your GP or a clinical professional.
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Primary sourcePreprint bioRxiv (Cold Spring Harbor Laboratory) · 2026-10-01TET loss of function selects for aneuploidies that confer a proliferative advantage