Frequent blood donors benefit from genetic changes in stem cells

Frequent blood donations have been correlated to favourable genetic changes that allow for healthy cell growth.

Researchers at the Francis Crick Institute, London, and the German Cancer Research Centre, Heidelberg, Germany, studied a group of older men who donated blood frequently (three or more times a year over 40 years), compared to similarly aged men who donate blood less frequently (less than five times total). Their findings, published in Blood, showed frequent donors had a mutation in the gene DNMT3A, and this change allowed cells to grow normally when challenged to different chemical environments.

'Our work is a fascinating example of how our genes interact with the environment and as we age,' said Professor Dominique Bonnet, group leader of the Haematopoietic Stem Cell Laboratory at the Francis Crick Institute and one of the senior authors 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 favours mutations that further promote stem cell growth rather than disease.'

Blood donation removes around ten percent of the circulating blood in a person's body. This puts a manageable challenge on stem cells in bone marrow that manufacture new red blood cells. During this process mutations can be introduced in DNA as cells divide and replicate. Typically, this process happens with age but is induced more frequently with blood donations. Mutations can have a negative effect on overall health but can also be neutral or favourable. It was already known that some mutations to DNMT3A are pre-leukaemic. The researchers conducted further testing to determine the favourability of the frequent donor DNMT3A mutation.

The researchers used the CRISPR approach to genome editing to change human stem cells to express the new DNMT3A mutation or a known DNMT3A pre-leukaemic mutation. They then grew the cells in two different chemical environments: one to mimic blood donation and one to mimic infection. The frequent donor mutation cells were able to grow normally, whereas the pre-leukaemic mutation cells did not.

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

Small sample sizes in voluntary studies may give rise to a phenomenon known as the healthy donor effect. In this case, the 217 men in the study who donated blood frequently may be healthier than the 212 men in the study that had less frequent blood donations. The authors hope that their study will inspire larger studies to investigate the genetics of frequent blood donors.