Regular Blood Donors Develop ‘Super Cells’ That Could Help Fight Disease todayheadline

New study finds frequent blood donation may select for beneficial genetic changes

The human body is remarkably adaptable, and nowhere is this more evident than in the response of long-term blood donors, according to striking new research from the Francis Crick Institute. Scientists have discovered that people who donate blood regularly develop unique genetic changes in their blood stem cells that appear to be beneficial rather than harmful.

The study, published this month in the journal Blood, analyzed samples from more than 200 frequent donors—individuals who had given blood three times a year for up to 40 years, totaling over 120 donations—and compared them with samples from people who had donated blood fewer than five times.

What they found challenges conventional understanding of how our blood cells change as we age. While all humans naturally accumulate mutations in their blood stem cells over time, the pattern of these mutations differed significantly between regular donors and non-donors.

A Natural Experiment in Human Biology

When someone donates blood, their body must quickly replace what was lost. This triggers bone marrow stem cells to increase production of new blood cells—essentially a form of controlled stress that occurs repeatedly in regular donors.

This recurring process appears to create an environment that favors certain genetic mutations over others, specifically selecting for changes that help cells respond efficiently to blood loss while potentially weeding out more problematic mutations.

“Our work is a fascinating example of how our genes interact with the environment and as we age,” explains Dominique Bonnet, Group Leader of the Haematopoietic Stem Cell Laboratory at the Crick and senior author of the study. “Activities that put low levels of stress on blood cell production allow our blood stem cells to renew and we think this favors mutations that further promote stem cell growth rather than disease.”

The DNMT3A Connection

Both donor groups showed mutations in a gene called DNMT3A, which is known to be altered in blood cancers like leukemia. However, the specific changes to this gene in frequent donors occurred in different regions than those typically associated with cancer development.

To further investigate these differences, the research team used genetic editing techniques to introduce both types of DNMT3A mutations—those found in frequent donors and those associated with leukemia—into human stem cells in the laboratory.

When these cells were exposed to erythropoietin (EPO), a hormone that surges after blood donation to stimulate red blood cell production, the cells with donor-type mutations thrived. Conversely, when exposed to inflammatory chemicals that mimic infection, these same cells struggled to grow. The opposite pattern emerged for cells carrying the leukemia-associated mutations.

The Mouse Model Confirmation

Taking their investigation further, the researchers transplanted human stem cells carrying both types of mutations into mice. Some of these mice then had blood removed and received EPO injections to simulate the physiological stress of blood donation.

The results were clear: cells with the frequent donor mutations grew normally under control conditions and efficiently produced red blood cells under stress conditions, without becoming cancerous. In sharp contrast, the cells with pre-leukemic mutations drove a pronounced increase in white blood cells regardless of conditions—a potential warning sign for cancer development.

Implications and Cautions

While these findings suggest that regular blood donation may create selective pressure against pre-cancerous mutations, the researchers are careful not to overstate their conclusions.

“Our sample size is quite modest, so we can’t say that blood donation definitely decreases the incidence of pre-leukemic mutations and we will need to look at these results in much larger numbers of people,” Bonnet notes. “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.”

Hector Huerga Encabo, postdoctoral fellow at the Crick and first joint author of the study with Darja Karpova from the DFKZ in Heidelberg, explains the significance: “We know more about preleukemic mutations because we can see them when people are diagnosed with blood cancer. We had to look at a very specific group of people to spot subtle genetic differences which might actually be beneficial in the long-term.”

Looking Forward

The research team is now focused on determining exactly how these different types of mutations influence leukemia development—or prevent it. “We’re now aiming to work out how these different types of mutations play a role in developing leukaemia or not, and whether they can be targeted therapeutically,” says Huerga Encabo.

This study opens fascinating possibilities for understanding how lifestyle choices might influence our genetic destiny. Regular, mild physiological stresses—like those experienced during blood donation—may actually help maintain healthier blood stem cell populations as we age.

While more research is needed before drawing definitive conclusions about blood donation’s protective effects, the study adds to growing evidence that small, regular challenges to our physiological systems may have unexpected benefits.

The research was made possible through collaboration between the Francis Crick Institute, Andreas Trumpp’s group at the DFKZ in Heidelberg, and Halvard Boenig’s group from the German Red Cross Blood Donation Service Centre in Frankfurt—highlighting the international effort required to understand these complex biological processes.

For the approximately 6.8 million blood donors in the United States alone, this research provides an intriguing glimpse into how their generosity might be benefiting not only recipients but potentially their own long-term health as well.