MechanismsHumans20 patientsCase series

Donor TET2 variant linked to lower stem cell transplant survival

Recipients whose donors carried a TET2 Leu1721Trp variant lived a median of 14.3 months compared with 50.8 months for those with wild-type donors.

Figure 1. Mutational landscapes before and after matched-related donor transplantation.Mutational landscapes before and after matched-related donor transplantation.Giudice et al. · CC BY

International Journal of Molecular Sciences4 Oct 2026, 08:59 BST

In 20 adult transplant recipients and their related stem cell donors, researchers tracked clonal evolution before and after transplantation using a 30-gene panel. Post-transplant hematopoiesis was frequently driven by donor-derived clones, with DNMT3A emerging as the most prevalent mutated gene across the cohort. However, specific donor alterations carried clinical risks. Recipients whose donors carried the TET2 Leu1721Trp variant had significantly shorter overall survival than those with wild-type donors (median 14.3 months versus 50.8 months). In contrast, the re-emergence of recipient-derived clones, especially oncogenic DNMT3A mutations, frequently preceded graft failure or leukemia relapse.

Why it matters

Clonal hematopoiesis expands with age and is often considered clinically neutral in healthy stem cell donors. These findings suggest that specific age-associated donor mutations could negatively shape hematopoietic reconstitution and patient survival.

Caveats

This study was a retrospective, single-center case series of only 20 recipient-donor pairs, meaning the survival links remain hypothesis-generating. Larger prospective cohorts are needed to verify whether donor TET2 variants consistently impair post-transplant outcomes.