Beneficial genetic changes observed in regular blood donors

Understanding the differences in the mutations that accumulate in our blood stem cells as we age It is important to understand how and why blood cancers develop and, hopefully, how to intervene before the start of clinical symptoms.

As we age, stem cells in the bone marrow naturally accumulate mutations and with this, we see the appearance of clones, which are groups of blood cells that have a slightly different genetic composition. Sometimes, specific clones can lead to blood cancers such as leukemia.

When people donate blood, stem cells in the bone marrow make new blood cells to replace lost blood and this stress drives the selection of certain clones.

In research published today in BloodThe CRICK team, in collaboration with DFKZ scientists in Heidelberg and the blood donation center of the German Red Cross, analyzed blood samples taken from more than 200 frequent donors, people who had donated blood three times more than 40 years, more than 120 times in total, and sporadic control donors who had donated blood less than five times in total.

The samples of both groups showed a similar level of clonal diversity, but the composition of blood cell populations was different.

For example, both sample groups contained clones with changes in a gene called DNMT3A, which is known to be mutated in people who develop leukemia. Interestingly, the changes in this gene observed in frequent donors were not in the areas that are known to be pre -alukémica.

To understand this better, CRICK researchers edited DNMT3A in human stem cells in the laboratory. They induced the genetic changes associated with leukemia and also the non -preleucemic changes observed in the frequent donor group.

They cultivated these cells in two environments: one that contains erythropoietin (EPO), a hormone that stimulates the production of red blood cells that increases after each blood donation, and another that contains inflammatory chemicals to replicate an infection.

The cells with the mutations commonly observed in frequent donors responded and grew in the environment that contained EPO and failed to grow in the inflammatory environment. The opposite was observed in the cells with mutations that are known to be preleukemics.

This suggests that the DNMT3A mutations observed in frequent donors are mainly responding to the physiological loss of blood associated with blood donation.

Finally, the team transplanted the human stem cells that carry the two types of mice mutations. Some of these mice took his blood and then received EPO injections to imitate the stress associated with blood donation.

Cells with frequent donors mutations normally grew in control conditions and promoted the production of red blood cells under stress, without the cells becoming cancerous. In contrast, preleukemic mutations promoted a pronounced increase in white blood cells both under control conditions and stress.

Researchers believe that regular blood donation is a type of activity that selects mutations that allow cells to respond well to blood loss, but do not select pre -elkhemic mutations associated with blood cancer.

Dominique Bonnet, group leader of the hematopoietic stem cell laboratory in CRICK, and the main author said: “Our work is a fascinating example of how our genes interact with the environment and, as we get old. favors promote the growth of the estimated cells instead of the disease.

“Our sample size is quite modest, so we cannot say that blood donation definitely decreases the incidence of pre-leucemic mutations and we will have to analyze these results in a much greater number of people. It could effects is fascinating. ” “It is reflected in its blood cell clones.

Héctor Huerga Embabo, postdoctoral member in the hematopoietic stem cell laboratory in the Crick, and the first joint author with Darpova Del DFKZ in Heidelberg, said: “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 detect subtle genetic differences that could actually be beneficial in the long term. We now have the objective of determining how these different types of mutations play a role in the development of leukemia or not, and if they can be therapeutically directed.”

This work was possible thanks to the collaboration with the Andreas Trumpp group in the DFKZ in Heidelberg and the Halvard Boenig group of the Blood Donation Services Center of the German Red Cross in Frankfurt.