Donating Blood Could Decrease the Risk of Developing Leukemia

 A Medical XPress article from March 11 presents new data about the genetics of blood stem cells in relation to blood donations. The new research completed at the Francis Crick Institute looked at genetic changes in stem cells after individuals donated blood. There were two groups studied, one group consisted of individuals who donated blood often (3x per year for 40 years) and the other group consisted of individuals who had donated blood less than a total of five times. After blood is drawn, stem cells have to replenish the supply and the researchers were interested to see how genetic mutations of stem cells differed between the two groups. The findings were that both groups had mutations to the DNMT3A gene which is common in leukemia patients. However, in the frequent donors, the mutation was not in the preleukemic position. When the stem cells were injected into mice, the frequent donor stem cells behaved normally while the stem cells from not frequent donors resulted in the emergence of leukemia. 

According to Medicine Plus, a DNMT3A gene mutation can lead to cytogenetically normal acute myeloid leukemia (CN-AML). One-third of CN-AML cases result from a genetic mutation but are somatic and therefore not inherited. Although the Francis Crick Institute researchers urge a larger study to confirm their results, understanding how genetic changes in stem cells arise could help with leukemia treatment in the future. 

Links

https://medicalxpress.com/news/2025-03-beneficial-genetic-regular-blood-donors.html

https://medlineplus.gov/genetics/gene/dnmt3a/#conditions

Sickle Cell Gene Therapy May Cause Cancer Linked Mutations

 There are forms of gene therapy that has the potential to benefit patients with genetic blood disorders. There is a study on individuals in a trial for sickle cell disease that suggests  key process within giving out the treatment might cause mutation that turn blood stem cells cancerous. In a very recent study that was lead by the University of York reported that  six patients involved in treatment for sickle cell gene therapy had showed signs of mutations that are linked with the development of cancer. Scientists responsible for the study says that this case needs more of a long-term study so they can understand and determine how the cells continue to evolve. Sickle Cell disease is where an inherited disorder in which causes pathological changes to an individual's hemoglobin. This is where the disease causes red blood cells to harden and obtain the "sickle" shape and die. With this, gene therapy can alter an individual's genes in a certain way that corrects the mutation or makes they can express a different, healthy form of hemoglobin. 

    Researchers paired whole-genome sequencing with new methods to follow and compare the DNA of blood stem cells in patients before and also after they undergo their treatment. After the study they were able to find that there were numerous driver mutations that have been linked to blood cancer. The researchers also describe that the treatment itself is not causing the mutations, but they say it appears to come from one of the earlier parts of the process. As described in the beginning they would need to undergo further research and study and identify how the cells evolve like that. 

Links:

https://www.fiercebiotech.com/research/sickle-cell-gene-therapy-process-may-cause-cancer-linked-mutations-blood-stem-cells

https://www.hopkinsmedicine.org/health/conditions-and-diseases/sickle-cell-disease#:~:text=Sickle%20cell%20disease%20is%20an%20inherited%20blood%20disorder%20marked%20by,causing%20painful%20and%20damaging%20complications.

Alcohol Damages Mouse DNA

A metabolite of alcohol known as acetaldehyde, which occurs naturally at low levels, causes double-stranded breaks in the DNA of mouse blood stem cells, according to a study published (January 3) in Nature. Unrepaired breaks can lead to large deletions and chromosome rearrangements, and the mutations are passed on to daughter cells that make up the blood.

Normally, the enzyme aldehyde dehydrogenase 2 (ALDH2) quickly oxidizes acetaldehyde into acetate, which cells use as a source of energy. But many people, including millions in Southeast Asia, carry mutations in the ALDH2 gene that causes the accumulation of acetaldehyde. These people, who are known to have an increased risk of developing esophageal cancer, may also be more susceptible to blood cancers, if the new results hold true in humans: ALDH2­ knockout mice suffered four times as much DNA damage as their wildtype counterparts after alcohol consumption, according to the study.

Research provides very strong evidence that an alcohol metabolite causes DNA damage to the important stem cells that go on to make tissues.

https://www.the-scientist.com/?articles.view/articleNo/51249/title/Alcohol-Damages-Mouse-DNA/

https://www.nature.com/articles/nature25154