Regular blood donation could promote beneficial genetic changes

Frequent blood donors may have genetic changes that promote the production of new, non-cancerous cells.

Donating blood can save someone’s life; now researchers have discovered that it could potentially save yours too. Researchers at the Francis Crick Institute (London, UK), in collaboration with the German Cancer Research Center (DFKZ; Heidelberg, Germany) and the German Red Cross Blood Donation Center (Berlin, Germany), have identified mutations in blood stem cells of regular blood donors that promote stem cell growth rather than disease.

Over time, bone marrow stem cells, known as hematopoietic stem cells (HSCs), accumulate mutations. This leads to the emergence of clones, which are groups of blood cells with slightly different genetic makeup. In some cases, specific clones can lead to blood cancers like leukemia. When people donate blood, HSCs work to produce new blood cells to replace those that have been lost, and this drives the selection of certain clones.

To investigate if donating blood affects HSCs and clones, the researchers used next-generation sequencing to analyze blood samples from over 200 frequent donors (FDs) – people who donated blood more than 120 times – and sporadic control donors (CDs) – people who donated less than five times in total.

They found that both groups showed a similar level of clonal diversity; however, the genetic makeup of the blood cell populations differed. While both groups displayed clones with mutations to DNMT3A – a gene mutated in people with leukemia – the FD mutations were not in the areas known to be preleukemic.

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To better understand the mutations, the researchers used CRISPR to edit DNMT3A in HSCs in vitro, introducing mutations associated with leukemia to some and non-preleukemic mutations seen in the FDs to others. They cultured these cells in two environments: one with erythropoietin (EPO), a hormone that stimulates red blood cell production and is increased after blood donations, and another with inflammatory chemicals to simulate an infection.

The cells with the FD mutations grew in the EPO-containing cultures but failed to grow in the inflammatory culture, while the opposite was seen in the cells with preleukemic mutations. This suggests that the FD DNMT3A mutations mainly respond to the physiological blood loss associated with blood donation.

The team transplanted the mutated human HSCs into mice, removing blood from some of them and injecting them with EPO to simulate the stress of blood donation. The HSCs with the FD mutations grew normally in control conditions and promoted red blood cell production under stress, without cells becoming cancerous. The HSCs with preleukemic mutations, on the other hand, drove a pronounced increase in white blood cells in both control and stress conditions.

“Our work is a fascinating example of how our genes interact with the environment and as we age,” commented senior author Dominique Bonnet (The Francis Crick Institute). “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 researchers acknowledge that the small sample size means they can’t say for definite that regular blood donation decreases the incidence of preleukemic mutations. They are now looking at how the mutations influence leukemia development and whether they can be targeted therapeutically.