Donating blood regularly could make the donor’s blood cells healthier and potentially more competitive against blood cells with leukemia-causing mutations.
Hector Huerga Encabo and his colleagues at The Francis Crick Institute in London
analyzed genetic data extracted from blood cells donated by 217 male volunteers in Germany, aged between 60 and 72, with a history of extensive blood donation (>100 life-time donations) to investigate the phenomenon of clonal hematopoiesis (CH). No significant difference in the overall incidence of CH was found in frequent donors compared to 212 sporadic donors (<10 life-time donations). However, upon deeper analysis of mutations in DNMT3A, the most commonly affected gene in CH, they observed distinct mutational patterns between the frequent donors and age/sex matched control donor cohorts.
The investigators found that frequent blood donors were more likely to have blood cells carrying certain mutations in a gene called DNMT3A.
To understand this difference, the team genetically engineered human blood stem cells – which give rise to all blood cells in the body – with these mutations and added them to lab dishes along with unmodified cells. In order to mimic the effects of blood donation, they also added a hormone called EPO, which the body produces following blood loss, to some of the dishes. A month later, the cells with the frequent-donor mutations had grown 50 per cent faster than those without the mutations, but only in the dishes containing EPO. Without this hormone, both cell types grew at a similar rate.
“It suggests that with every blood donation, you’re going to have a burst of EPO in your system and this is going to favor the growth of cells with these DNMT3A mutations,” said Encabo. To investigate whether having more of these mutated blood cells is beneficial, the team mixed them with cells carrying mutations that raise the risk of leukemia, and again found that, in the presence of EPO, the frequent-donor cells substantially outgrew the others, and were better able to produce red blood cells. “This suggests that the DNMT3A mutations are beneficial and might suppress the growth of cancerous cells” added Encabo.
“It’s like the donation of blood is providing a selection pressure to enhance the fitness of your stem cells and their ability to replenish,” said Ash Toye at the University of Bristol, UK. “Not only could you save someone’s life, but maybe you are enhancing the fitness of your blood system.
”Further work is needed to verify if this is really the case, says Marc Mansour at University College London, as lab experiments provide a highly simplified picture of what happens in the body. “This needs to be validated in a much larger cohort, across different ethnicities, across females and other age groups,” says Mansour. He also points out that donors without the DNMT3A mutation may not see this benefit.
