Researchers at the Francis Crick Institute have identified genetic changes in blood stem cells from frequent blood donors that support the production of new, non-cancerous cells.
Understanding the differences in the mutations that accumulate in our blood stem cells as we age is important to understand how and why blood cancers develop and hopefully how to intervene before the onset of clinical symptoms.
As we age, stem cells in the bone marrow naturally accumulate mutations and with this, we see the emergence of clones, which are groups of blood cells that have a slightly different genetic makeup. Sometimes, specific clones can lead to blood cancers like leukemia.
When people donate blood, stem cells in the bone marrow make new blood cells to replace the lost blood and this stress drives the selection of certain clones.
In research published Blood, the team at the Crick, in collaboration with scientists from the DFKZ in Heidelberg and the German Red Cross Blood Donation Center, analyzed blood samples taken from over 200 frequent donors—people who had donated blood three times a year over 40 years, more than 120 times in total—and sporadic control donors who had donated blood less than five times in total.
Samples from both groups showed a similar level of clonal diversity, but the makeup of the blood cell populations was different.
For example, both sample groups contained clones with changes to a gene called DNMT3A, which is known to be mutated in people who develop leukemia. Interestingly, the changes to this gene observed in frequent donors were not in the areas known to be preleukemic.
To understand this better, the Crick researchers edited DNMT3A in human stem cells in the lab. They induced the genetic changes associated with leukemia and also the non-preleukemic changes observed in the frequent donor group.
They grew these cells in two environments: one containing erythropoietin (EPO), a hormone that stimulates red blood cell production which is increased after each blood donation, and another containing inflammatory chemicals to replicate an infection.
The cells with the mutations commonly seen in frequent donors responded and grew in the environment containing EPO and failed to grow in the inflammatory environment. The opposite was seen in the cells with mutations known to be preleukemic.
This suggests that the DNMT3A mutations observed in frequent donors are mainly responding to the physiological blood loss associated with blood donation.
Finally, the team transplanted the human stem cells carrying the two types of mutations into mice. Some of these mice had blood removed and then were given EPO injections to mimic the stress associated with blood donation.
The cells with the frequent donor mutations grew normally in control conditions and promoted red blood cell production under stress, without cells becoming cancerous. In sharp contrast, the preleukemic mutations drove a pronounced increase in white blood cells in both control or stress conditions.
The researchers believe that regular blood donation is one type of activity that selects for mutations that allow cells to respond well to blood loss, but does not select the preleukemic mutations associated with blood cancer.
Dominique Bonnet, Group Leader of the Hematopoietic Stem Cell Laboratory at the Crick, and senior author, said, “Our work is a fascinating example of how our genes interact with the environment and as we age. 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.
“Our sample size is quite modest, so we can’t say that blood donation definitely decreases the incidence of pre-leukemic mutations and we will need to look at these results in much larger numbers of people. 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.”
Hector Huerga Encabo, postdoctoral fellow in the Hematopoietic Stem Cell Laboratory at the Crick, and first joint author with Darja Karpova from the 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 spot subtle genetic differences which might actually be beneficial in the long-term. We’re now aiming to work out how these different types of mutations play a role in developing leukemia or not, and whether they can be targeted therapeutically.”
More information: Karpova, D. et al. Clonal Hematopoiesis Landscape in Frequent Blood Donors, Blood (2025). DOI: 10.1182/blood.2024027999

News
3D-printed implant offers a potential new route to repair spinal cord injuries
A research team at RCSI University of Medicine and Health Sciences has developed a 3-D printed implant to deliver electrical stimulation to injured areas of the spinal cord, offering a potential new route to [...]
Nanocrystals Carrying Radioisotopes Offer New Hope for Cancer Treatment
The Science Scientists have developed tiny nanocrystal particles made up of isotopes of the elements lanthanum, vanadium, and oxygen for use in treating cancer. These crystals are smaller than many microbes and can carry isotopes of [...]
New Once-a-Week Shot Promises Life-Changing Relief for Parkinson’s Patients
A once-a-week shot from Australian scientists could spare people with Parkinson’s the grind of taking pills several times a day. The tiny, biodegradable gel sits under the skin and releases steady doses of two [...]
Weekly injectable drug offers hope for Parkinson’s patients
A new weekly injectable drug could transform the lives of more than eight million people living with Parkinson's disease, potentially replacing the need for multiple daily tablets. Scientists from the University of South Australia [...]
Most Plastic in the Ocean Is Invisible—And Deadly
Nanoplastics—particles smaller than a human hair—can pass through cell walls and enter the food web. New research suggest 27 million metric tons of nanoplastics are spread across just the top layer of the North [...]
Repurposed drugs could calm the immune system’s response to nanomedicine
An international study led by researchers at the University of Colorado Anschutz Medical Campus has identified a promising strategy to enhance the safety of nanomedicines, advanced therapies often used in cancer and vaccine treatments, [...]
Nano-Enhanced Hydrogel Strategies for Cartilage Repair
A recent article in Engineering describes the development of a protein-based nanocomposite hydrogel designed to deliver two therapeutic agents—dexamethasone (Dex) and kartogenin (KGN)—to support cartilage repair. The hydrogel is engineered to modulate immune responses and promote [...]
New Cancer Drug Blocks Tumors Without Debilitating Side Effects
A new drug targets RAS-PI3Kα pathways without harmful side effects. It was developed using high-performance computing and AI. A new cancer drug candidate, developed through a collaboration between Lawrence Livermore National Laboratory (LLNL), BridgeBio Oncology [...]
Scientists Are Pretty Close to Replicating the First Thing That Ever Lived
For 400 million years, a leading hypothesis claims, Earth was an “RNA World,” meaning that life must’ve first replicated from RNA before the arrival of proteins and DNA. Unfortunately, scientists have failed to find [...]
Why ‘Peniaphobia’ Is Exploding Among Young People (And Why We Should Be Concerned)
An insidious illness is taking hold among a growing proportion of young people. Little known to the general public, peniaphobia—the fear of becoming poor—is gaining ground among teens and young adults. Discover the causes [...]
Team finds flawed data in recent study relevant to coronavirus antiviral development
The COVID pandemic illustrated how urgently we need antiviral medications capable of treating coronavirus infections. To aid this effort, researchers quickly homed in on part of SARS-CoV-2's molecular structure known as the NiRAN domain—an [...]
Drug-Coated Neural Implants Reduce Immune Rejection
Summary: A new study shows that coating neural prosthetic implants with the anti-inflammatory drug dexamethasone helps reduce the body’s immune response and scar tissue formation. This strategy enhances the long-term performance and stability of electrodes [...]
Scientists discover cancer-fighting bacteria that ‘soak up’ forever chemicals in the body
A family of healthy bacteria may help 'soak up' toxic forever chemicals in the body, warding off their cancerous effects. Forever chemicals, also known as PFAS (per- and polyfluoroalkyl substances), are toxic chemicals that [...]
Johns Hopkins Researchers Uncover a New Way To Kill Cancer Cells
A new study reveals that blocking ribosomal RNA production rewires cancer cell behavior and could help treat genetically unstable tumors. Researchers at the Johns Hopkins Kimmel Cancer Center and the Department of Radiation Oncology and Molecular [...]
AI matches doctors in mapping lung tumors for radiation therapy
In radiation therapy, precision can save lives. Oncologists must carefully map the size and location of a tumor before delivering high-dose radiation to destroy cancer cells while sparing healthy tissue. But this process, called [...]
Scientists Finally “See” Key Protein That Controls Inflammation
Researchers used advanced microscopy to uncover important protein structures. For the first time, two important protein structures in the human body are being visualized, thanks in part to cutting-edge technology at the University of [...]