Donating your blood is a humanitarian activity that can save lives. According to the American Red Cross, a unit of blood is required once every two seconds to save the lives of trauma victims, surgery patients, and individuals suffering from various chronic illnesses.
An estimated 6.5 million Americans donate their blood at least once per year (2021 data). That translates to around 16 million blood components—red blood cells and platelets—used for transfusions.
While approximately 205 million Americans (62% of the total population) are eligible to donate blood, less than 5% show any interest. A new study by the Francis Crick Institute might prove beneficial in attracting more donors in the future.
According to the results of the study, published in the very aptly named journal Blood, frequent blood donors have more beneficial mutations in their blood that may reduce their risk of acquiring blood cancers like leukemia.
Basic Premise of the Francis Crick Study
The Francis Crick Institute is a London-based biomedical research center active since 2016. This particular study also involved scientists from the German Cancer Research Center (DFKZ) in Heidelberg, Germany. The blood samples were provided by the German Red Cross.
For research purposes, most studies classify a frequent blood donor as someone who donates blood at least three times a year. The Francis Crick team set the threshold even higher at 40 years of continuous blood donations (120+ lifetime donations).
Blood samples of 200 frequent blood donors were compared to a control group of donors who had only done sporadic blood donations, with an upper limit of just five-lifetime donations. The analysis focused on one area in particular – clonal mutations.
Understanding Clonal Mutations
A clonal mutation is a random DNA mutation that occurs in any cell in organisms that have regenerating/renewing cells (including humans). Clonal mutations are natural processes that can occur during the routine process of cell division.
If the mutation gives that particular cell some kind of growth advantage or boost, it can quickly create daughter cells (clones) that outcompete other “normal” cells. While in many instances the mutation may be benign, clonal mutations can also lead to cancerous tumors.
Clonal mutations are an area of special interest for blood cancer research. All blood cells are derived from a single stem cell type in the bone marrow – the Hematopoietic Stem Cells or HSCs. They are the master cells that divide into red cells, white cells, and platelets.
If there is a clonal mutation in an HSC, it can quickly affect the entire bloodstream and give rise to various cancers like leukemias, lymphomas, and other forms of neoplasms. Vulnerable genes that contribute to cancer development include JAK2, FLT3, and DNMT3A.
The Differences in DNMT3A Mutations Between Donor Groups
The researchers analyzed and compared blood samples of both cohorts for changes in clonal mutations. Both frequent donors and the control group donors had similar levels of clonal diversity in their blood samples.
In other words, the frequency of mutations in the HSCs is not affected by the frequency of blood donations. All individuals expressed a similar level of clonal mutations which are caused by the natural side effects of aging.
However, when it comes to the actual nature of the mutations, there were some notable differences. One gene stood out in the results – the DNMT3A gene, which is commonly associated with leukemia.
In the control group of sporadic blood donors, the DNMT3A mutations were in locations that are known to be pre-leukemic. Meaning, that these were mutations that had a chance of eventually developing into leukemia in the future.
Meanwhile, DNMT3A mutations were present in frequent donors in other regions of the gene’s DNA. These mutations were not commonly associated with an increased risk of leukemia. The differences are decidedly quite subtle, but they were there.
The Potentially Beneficial Impact of Blood Loss on Clonal Mutations
During a blood donation, the staff will draw out at least one pint (around 450ml) of blood from a donor. The average adult has around 10 to 11 pints of blood in their body at any time. A donation involves losing around a 10th of your total blood.
In terms of raw physiological impact on the body, a blood donation is essentially a form of blood loss. The body responds to blood loss due to injury or trauma by releasing a hormone called erythropoietin (EPO). Its role is to stimulate the production of red blood cells.
During further lab tests, DNMT3A mutations in frequent donors responded well to EPO, triggering the accelerated creation of additional clonal cells. In mice, the frequent donor mutations responded well to stress (inflammation) without any signs of cancer genesis.
In stark contrast, the pre-leukemic mutations in the control group responded poorly to EPO. Mice with transplanted human stem cells showed elevated levels of white blood cell production when exposed to stress, mimicking the early stages of disease progression.
The Key Takeaways and Caveats
The study is fascinating not because it offers up any concrete solutions to treating or catching blood cancers early, it does not do any of that. However, it offers us a fascinating glimpse into the impact incremental exposure to low-level stress can have on our DNA.
Think about exercise – each session at the gym delivers a healthy dose of stress to the body’s muscles, stimulating growth, increased strength, and stamina gains. Likewise, regular blood donations deliver stimulatory stress to the HSCs.
Forcing the cells to enter the cell division cycle more often in the presence of EPO might be encouraging specific clonal mutations that improve overall resilience and cellular regeneration. Giving them frequent “workouts,” in other words.
The major caveat here is the size of the study. We cannot draw many definitive conclusions from a sample size of just 200 frequent donors. What if these are individuals who take better care of their health than the regular population? The sample size is too small.
However, there is no doubt that the study does throw up some interesting implications. Further research involving a larger group of blood donors is needed. It could help us learn much more about the role played by mutations in blood cancer genesis.
