Conventional blood donors develop “super cells” which may help fight disease

New research finds that frequent donations of blood may choose beneficial genetic changes

According to shocking research by the Francis Crick Institute, the body is very adaptable and there is no more obvious response than long-term blood donors. Scientists have found that people who donate blood regularly develop unique genetic changes in vascular 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 common donors—individuals receive blood donations three times a year for up to 40 years, totaling more than 120 years of donations, and compared them with samples from people who donated five less blood.

The challenges they found were challenges that change our blood cells with age. Although all humans naturally accumulate mutations in their blood stem cells over time, the patterns of these mutations vary significantly between conventional and non-donors.

Natural experiments in human biology

When someone donates blood, their bodies must quickly replace the lost. This triggers bone marrow stem cells to increase production of new blood cells, which is actually a form of controlled stress that occurs repeatedly in conventional donors.

This often occurring process seems to create an environment favoring mutations in some genes over others, specifically choosing changes that help cells respond effectively to blood loss, while potentially eliminating more problematic mutations.

“Our work is a fascinating example of how our genes interact with the environment and our age,” explains Dominique Bonnet, group leader and senior author of the study at Crick’s Hematopoietic Stem Cell Laboratory. “The lower stress activity on blood cells allows our blood stem cells to renew, which we believe is conducive to further promoting stem cell growth rather than mutations in the disease.”

DNMT3A connection

Both donor groups showed mutations in a gene called DNMT3A, which is known to alter mutations in hematologic cancers such as leukemia. However, in common regions of donors associated with cancer development, specific changes in this gene occur in different regions.

To further investigate these differences, the team introduced two types of DNMT3A mutations (discovered in frequently occurring donors and donors associated with leukemia-human stem cells in the laboratory.

When these cells are exposed to erythropoietin (EPO), a hormone surges after blood donation to stimulate red blood cell production, and cells with donor-type mutations thrive. Instead, these same cells strive to grow when exposed to inflammatory chemicals that mimic the infection. The opposite pattern appears in cells carrying leukemia-related mutations.

Mouse model confirmation

The researchers who further studied their transplanted human stem cells carrying two mutations into mice. Some of the mice then removed the blood and received an EPO injection to simulate the physiological stress of blood donation.

The results were obvious: cells with frequent donor mutations were grown normally under control conditions and red blood cells were effectively produced under stress conditions without cancer. In sharp contrast, cells with pre-leukocyte mutations lead to a significant increase in leukocytes, which is a potential warning sign of cancer development regardless of conditions.

Meaning and precautions

Although these findings suggest that regular donations may put selective pressure on precancerous mutations, researchers are careful not to exaggerate their conclusions.

“Our sample size is very moderate, so we can’t say that donating blood will certainly reduce the incidence of pre-gastronomy mutations, and we will need to study these results with more people,” Bonnet noted. “It is possible that people who donate blood are more likely to be healthy if they qualify, which is also reflected in their blood cell clones.”

Academician Hector Huerga, a postdoctoral fellow at Crick and first author of Darja Karpova of DFKZ in Heidelberg, explains this: “We know more about preleukemic mutations because when people are diagnosed with blood cancer, we can see them. We have to study a very specific population to find subtle genetic differences that can actually be beneficial in the long run.”

expect

Now, the research team is committed to determining exactly how these different types of mutations affect the development or blocking of leukemia. “Our goal now is to determine how these different types of mutations play a role in the development of leukemia and whether they can target treatments,” Huerga Accabo said.

This study opens fascinating possibilities to understand how lifestyle choices affect our genetic fate. Conventional, mild physiological stresses, such as those experienced during blood donation, may actually help maintain a healthier population of blood stem cells as you age.

Although more research is needed before defining conclusions about the protective effects of blood donation, this study adds to increasing evidence that smaller challenges to our physiological system may bring unexpected benefits.

The study was achieved through collaboration between the Francis Crick Institute, the Andreas Trumpp group of DFKZ in Heidelberg, and the Halvard Boenig group from the German Red Cross Blood Donation Service in Frankfurt, which is highly visible from the international efforts required to understand these complex biological processes.

For approximately 6.8 million blood donors in the United States alone, this study benefits not only the recipients, but also their own long-term health.