Donor TET2 variant links to shorter transplant survival

In a retrospective study of 20 human adult stem cell transplant recipients and their related donors, researchers tracked clonal evolution using longitudinal targeted sequencing of a 30-gene panel. Post-transplant blood reconstitution was frequently driven by donor-derived clones, with DNMT3A mutations being the most prevalent across the cohort. However, donor genetic profiles directly affected recipient outcomes. Patients whose donors carried the TET2 Leu1721Trp variant experienced significantly worse overall survival than those receiving wild-type grafts. In addition, the reappearance of recipient-derived clones, specifically oncogenic DNMT3A mutations, frequently preceded graft failure or leukemia relapse. In contrast, five recipients received grafts from donors without detectable mutations or variants of uncertain significance. The findings suggest that while donor clonal hematopoiesis is often viewed as clinically neutral, specific variants alter post-transplant reconstitution and recipient survival.