Frequent blood donation may promote the growth of healthy blood cells without increasing the risk of preleukemic mutations, according to research published yesterday in
Blood. Investigators at the Francis Crick Institute, in collaboration with the German Cancer Research Center and the German Red Cross Blood Donation Center,
found that long-term blood donation influences the genetic makeup of blood stem cells in a way that supports red blood cell production.
Investigators analyzed blood samples from 217 male blood donors aged 60-69 years who had donated more than 120 times throughout their lives and compared them with samples from 212 sporadic donors with fewer than five lifetime blood donations. While both groups showed similar rates of clonal hematopoiesis, the researchers observed notable differences in the mutations affecting the DNMT3A gene, which is known to be mutated in people who develop leukemia. In frequent donors, DNMT3A mutations were found in regions not typically associated with leukemia, while sporadic donors were more likely to have mutations in leukemogenic regions of the gene.
In subsequent laboratory tests, investigators introduced DNMT3A mutations from both donor groups into human blood stem cells and exposed them to erythropoietin (EPO), a hormone that increases after blood loss and promotes red blood cell production. Mutations observed in frequent donors responded positively to EPO, promoting red blood cell growth. In contrast, preleukemic DNMT3A mutations responded to inflammatory signals and demonstrated a myeloid cell bias, which is often a precursor to malignancy.
Further testing in mice confirmed that the DNMT3A mutations prevalent in frequent donors facilitated healthy red blood cell production without promoting cancerous growth, while the preleukemic mutations drove increased white blood cell production.
According to the researchers, the findings suggest that frequent blood donation may create a selective pressure favoring stem cells with mutations that enhance red blood cell production, without increasing the risk of leukemia. However, they cautioned that the small sample size and potential “healthy donor effect” limit the study’s broader implications.
“Our sample size is quite modest, so we can’t say that blood donation definitely decreases the incidence of preleukemic mutations and we will need to look at these results in much larger numbers of people,” said Dominique Bonnet, PhD, senior author and group leader of the Crick’s hematopoietic stem cell laboratory. “It might be that people who donate blood are more likely to be healthy if they’re eligible, and this is also reflected in their blood cell clones. But the insight it has given us into different populations of mutations and their effects is fascinating.”
