Human blood cells, SEM
Credit: Science Photo Library/STEVE GSCHMEISSNER/Getty Images

New research lead by investigators at the Wellcome Sanger Institute has identified 17 additional age-related mutations in genes that drive the abnormal overgrowth of blood cells. The findings, published in Nature Genetics, give additional information about the genetic factors that influence clonal hematopoiesis, a process linked to aging and to an increased risk of developing a blood cancer.

In collaboration with Calico Life Sciences and the University of Cambridge, the Sanger team conducted a retrospective study of more than 200,000 people from the UK Biobank, looking for genes showing signals of “positive selection,” or age-related mutations that allow the cell population to expand over time.

From this, the researchers identified 17 genes that showed similar associations of already-known clonal hematopoiesis mutations driving the accumulation of mutant blood cell clones. The identification of these new genetic drivers provides researchers with new fertile ground for research aimed at better understanding the development of clonal hematopoiesis, how it influences development of disease, and potentially new diagnostic screening tools that can help identify patient risk of developing different forms of cancer and cardiovascular disease.

“While existing genetic tests have been valuable for early disease detection, our findings suggest there are opportunities to improve them further,” said co-first author of the study Michael Spencer Chapman, PhD, of the Wellcome Sanger Institute. “By incorporating these 17 additional genes linked to clonal hematopoiesis, we can enhance genetic testing methods to better identify risks of associated blood cancers and cardiovascular diseases.”

Clonal hematopoiesis is the result of cells’ genes accumulating age-related mutations over time. Some of these mutations confer a competitive growth advantage, which provides an avenue for these cells to grow and eventually outnumber healthy cells. The condition occurs when this positive selection for mutant cells happens in blood stem cells. Clonal hematopoiesis is known to be associated with age related diseases, as wells as blood cancers and cardiovascular conditions.

Previously, other research has pointed to roughly 70 other genes that were linked to clonal hematopoiesis. But the most recent observed cases of the condition have shown not one mutation in any of this group of driver genes, suggesting other genes are also involved in the process.

To help find these additional genetic drivers, the investigators used the data of more than 200,000 people in the UK Biobank to map out patterns of positive selection in the aging blood system. The identification of these new genes that influence accumulation of mutant cells clones in blood increased the known prevalence of clonal hematopoiesis by 18 percent in the UK Biobank cohort.

“With our newly identified genes, we now have a more complete picture to explore strategies for delaying or reversing abnormal mutant cell overgrowths in blood to promote healthier aging,” noted Nick Bernstein, co-first author of the study, formerly of Calico Life Sciences. “These genes seem to affect inflammation and immunity, important factors in conditions like heart disease and strokes. While interventions based on this research are still a long way off, it opens up possibilities for future treatments across a wide range of diseases.”

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