New evidence suggests ganciclovir may alter stem cell transplant patients’ DNA, but that transplanted stem cells do not. That’s according to a study by Researchers in the Van Boxtel group at the Princess Máxima Center for pediatric oncology.
The researchers analyzed the DNA of blood cells in nine patients who had undergone a hematopoietic stem cell transplant (HSCT). The team characterized the mutation burden of hematopoietic stem and progenitor cells (HSPCs) in these patients and their donors using whole-genome sequencing. They report that the majority of transplanted HSPCs did not display altered mutation accumulation.
However, in two HSCT recipients, there were multiple HSPCs with a specific genomic signature. The team writes that, based on their work this result may be due to a “unique mutational signature caused by the antiviral drug ganciclovir.” They used a machine learning approach to detect this signature.
The lead author of the study is J.K. de Kanter, and it appears in Cell Stem Cell.
Stem cell transplantation is an important part of treatment for some children with leukemia, but the exact effect of stem cell transplantation on DNA is not yet known. Currently, it is estimated that there are more than 500,000 HSCT survivors across the globe, and this number is expected to increase 5-fold by 2030.
In the course of their study, Van Boxtel’s team came across a small number of patients with a particular pattern of DNA mutations that they had not seen before. To further investigate, they analyzed data from more than 3,000 patients with cancer that had spread or with blood disorders using artificial intelligence software.
The scientists discovered nine more patients with this type of marker in their cancer. They noticed that all of these patients had been treated with the drug ganciclovir, which is used to treat serious viral infections in people with a severely weakened immune system, such as patients who have had a stem cell transplant. The team also discovered this DNA marker in adults with solid tumors who had had a kidney transplant earlier in life and were then treated with ganciclovir.
To investigate further, the team exposed cultured blood stem cells in the lab to ganciclovir. They saw that, indeed, the drug caused the same DNA marker. Ganciclovir also led to changes in genes known to cause cancer.
The team then tested another anti-virus drug, foscarnet, which is also used to treat viral infections after stem cell transplantation. Foscarnet did not cause the type of DNA changes they saw with ganciclovir.
Ruben van Boxtel, principal investigator at the Princess Máxima Center for pediatric oncology and leader of the study, said, “Thanks to new techniques to unravel the entire genetic make-up of tumors, we discovered that an antiviral drug could have a carcinogenic effect. “The exact effect of the scar that ganciclovir leaves behind in the DNA is still unclear. In what way these DNA changes can lead to cancer, and how strong that effect is, still needs to be investigated.”
Van Boxtel added that, “There are currently more than 30 of these types of anti-virus drugs on the market, which are used to fight infections with various viruses. Our new study underscores the need to investigate which of these agents are or aren’t harmful to the DNA of our cells.”