Frequent blood donation may foster genetic changes in blood stem cells that enhance red blood cell production without elevating pre-leukemic risks, according to a study in Blood by the Francis Crick Institute, German Cancer Research Center, and German Red Cross.
Study Details
The team analyzed 217 male donors aged 60-69 with over 120 lifetime donations versus 212 sporadic donors (fewer than five donations). Clonal hematopoiesis rates were comparable, but DNMT3A mutations the most common in such conditions differed: frequent donors had variants in non-leukemogenic regions.
Lab and Animal Validation
Using CRISPR-edited human stem cells, frequent-donor DNMT3A mutations expanded under erythropoietin (EPO) stimulation mimicking post-donation hormone surges promoting erythroid differentiation and red blood cell output. Pre-leukemic mutations (e.g., R882) favored myeloid bias and inflammation instead.
Mouse xenografts reinforced this: under simulated donation stress (blood removal + EPO), frequent-donor variants supported balanced, non-cancerous hematopoiesis, while pre-leukemic ones drove white blood cell overgrowth.
Broader Context and Limitations
Repeated phlebotomy creates selective pressure via bone marrow regeneration (2.5-4% erythropoiesis boost per donation), potentially favoring adaptive clones. Senior author Dr. Dominique Bonnet cautioned on the modest sample and "healthy donor effect": "Healthier people donate more, skewing clones fascinating insights, but larger studies needed."
This underscores donation safety amid global shortages, revealing lifestyle's role in stem cell evolution.
