Blood stem cells are vulnerable to DNA damage that can persist for several years, according to a new UK study which casts new light on the origins of blood cancers.
A team led by researchers at the Wellcome Sanger Institute, Cambridge, say this arises from a kind of DNA damage that leads to around 15 to 20% of the mutations in these cells. Even worse, they report, cells try to copy the damaged DNA, leading to further mistakes and multiple mutations from a single source of DNA damage.
The discoveries have emerged from a project that sought to identify the “family trees” of single cells from several individuals by studying patterns of shared mutations.
Reporting in Nature, the researchers say they found unexpected patterns of mutation inheritance. Although the study involved several kinds of cell, the researchers found the survival of damage to be particularly long-lasting in blood stem cells, lasting for up to three years.
They say this creates multiple opportunities for harmful mutations that could lead to cancer.
Researcher Dr Michael Spencer Chapman said: “With these family trees, we can link the relationships of hundreds of cells from one person right back to conception, meaning we can track back through the divisions each cell has gone through. It’s these large-scale, novel datasets that have led us to this unexpected finding that some forms of DNA damage can last for a long time without being repaired.”
Fellow researcher Emily Mitchell said: “It is unclear why this process is only found in blood stem cells and not other healthy tissues. Knowing that the DNA damage is long-lasting gives new routes to investigate what the damage actually is. As we continue to better understand the causes of mutations, we may one day be able to intervene and remove them.”
Source:
Spencer Chapman M, Mitchell E, Yoshida K, Williams N, Fabre MA, Ranzoni AM, Robinson PS, Kregar LD, Wilk M, Boettcher S, Mahbubani K, Saeb Parsy K, Gowers KHC, Janes SM, Ng SWK, Hoare M, Green AR, Vassiliou GS, Cvejic A, Manz MG, Laurenti E, Martincorena I, Stratton MR, Nangalia J, Coorens THH, Campbell PJ. (2025) “Prolonged persistence of mutagenic DNA lesions in somatic cells.” Nature, 15 January 2025, doi: 10.1038/s41586-024-08423-8.
Link: https://www.nature.com/articles/s41586-024-08423-8
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