Young stem cell donors harbor undetectable mutations linked to disease

January 15, 2020

A pilot study of 25 donor-recipient pairs reveals that healthy young donors of stem cells harbor previously undetected and potentially disease-causing mutations in their blood stem cells, which were transferred to unrelated recipients of the transplants. Although more comprehensive studies are needed, the findings imply that these mutations - which have been linked to post-transplant complications - are more prevalent in young donors than previously thought. Stem cell transplants can treat or even cure blood-related diseases such as enzyme deficiencies and some blood cancers. Studies have shown that stem cell donors over the age of 50 have accumulated at least some mutations in blood stem cells, a process referred to as clonal hematopoiesis. These mutations don't lead to immediate signs of disease, but recent research has connected them to serious conditions such as coronary artery disease and graft-versus-host disease in patients who receive the transplants. Wing Hing Wong and colleagues used advanced sequencing methods to study clonal hematopoiesis in adolescents and young adults, who make up 86% of eligible, unrelated stem cell donors. Among 25 matched donors and recipients, 11 of the donors (median age of 26) had clonal mutations that couldn't be detected with standard sequencing techniques, and 84% of these mutations were predicted to be pathogenic. Importantly, all of the mutations engrafted in the transplant recipients, and the clones expanded in the patients in the first 100 days after transplantation. The clinical implications of the findings remain to be further studied, said Wong. "Once we have a more comprehensive study, we might need to carefully screen donors for mutations that are otherwise undetectable, but are associated with clinical complications in recipients," he added.
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American Association for the Advancement of Science

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