Increase the risk of cancer? Notes from long -standing recipients
Increase the risk of cancer? Notes from long -standing recipients
Since the successful transplantation of the first blood-oriented stem cells more than 50 years ago, researchers have wondered whether this mutation-related cancer . A unique study 1 , which examined the long-lasting transplant recipients and their donors, showed that persons who receive donor stamp cells, do not seem to have an increased risk of such mutations.
The results are surprising, but calming, says Michael Spencer Chapman, hematologist at the Barts Cancer Institute in London.
"These are fantastic news for people who go through these therapies," says Alejo Rodriguez-Fraticelli, quantitative stem cell biologist at the Institute for Biomedical Research in Barcelona, Spain.
Blood -tapping or" hematopoetic "stem cells are progenitor cells that live in the bone marrow and originate from all types of blood cells. They are used to treat hundreds of thousands of people with blood cancer and bone marrow diseases. The
The latest study published this week in Science Translational Medicine examined mutations in specific genes that are associated with cancer. It has been suspected that these mutations could provide the hematopoetic cells a growth advantage for transplant recipients, which quickly divides and multiply while the recipient could age, and finally develop into leukemia. Some of the first transplants were carried out in the Fred Hutchinson Cancer Center from the end of the 1960s. In 2017, Masumi Ueda Oshima, clinical researcher, who studies aging after transplantation at the Fred Hutchinson Cancer Center in Seattle, Washington, and her colleagues, the recipients of these transplants and their donors to collect and compare blood samples, how the cells were aged. "It was really a big fan expedition," she says. The team collected blood samples from 32 individuals-16 donor-recipients-who had received their transplants between 7 and 46 years before. They used a highly sensitive technique to sequence genes that are known to acquire mutations that are connected to bone marrow cancer. The team members found cells with mutations in all healthy donors, even with those who were only 12 years old. The older the donor was, the more frequent the mutations in their blood, but overall the frequency remained low - only one of one million of the sequential base pairs. Then the researchers compared the mutation patterns in 11 donor-recipient pairs, for which they could access donor blood samples from the time of the transplant. They found similar mutation patterns in both groups. On average, mutations for donors with a rate of 2 % per year and for recipients with 2.6 % per year occurred. "Surprisingly, there are actually very few new mutations in the stem cells that arise from the transplant process," says Spencer Chapman. This indicates that the cells of transplant recipients age at a similar pace as that of their donors, and they have no increased risk of developing mutations that they could predispose for blood cancer. The fact that the mutations remain stable for so long after a transplant shows that "the regenerative ability of the hematopoetic system is really remarkable," says Ueda Oshima. rodriguez-fraticelli points out that the results are calming, but are based on a small number of individuals, which makes it difficult to draw general conclusions. Spencer Chapman observed similar results in a separate study of donor-recipient pairs 2 Preprint was published. His study comprised 10 transplant recipients who had received hematopoetic cells from their siblings between 9 and 31 years before. However, they not only examined changes in specific genes that are connected to cancer, but also extracted and cultivated hematopoetic cells in a laboratory and sequenced the entire genomes of individual cells. On average, they found that recipients only had more mutations than their donors, which only added 1.5 years of normal age structure - a similar statement as that of Ueda Oshima. When they and their colleagues searched for mutations that give the cells a growth advantage, they found that cells with only one of these mutations were found at similar levels for both recipients and donors. However, cells with two or more advantageous mutations were available in higher quantities for recipients than with donors. This result could help explain why in rare cases transplanted cells can develop tumors. But further work is required to better understand the implications of these aging processes regarding the risk of cancer and immune function, says Spencer Chapman. Both studies could have an impact on people who could have stem cell transplants and blood-based gene therapies for the treatment of Sichelzell anemia . More and more of these therapies “come to the mainstream” and are given to children who will be dependent on the transplanted cells, for example, for their lives, says Spencer Chapman. Ueda Oshima, M. et al. Sci. Transl. Med. 16, EADO5108 (2024). latest research
complex aging
Campbell, P. et al. Preprint at Research Square https://doi.org/10.21203/rs.3.rs-2868644/v1 (2023).