17 New Clonal Hematopoiesis Drivers Identified

An international team of researchers has identified 17 previously unknown genes that contribute to the abnormal proliferation of mutated blood cells as people grow older. This discovery, published in Nature Genetics, provides a more comprehensive understanding of the genetic factors underlying clonal hematopoiesis, a process linked to aging and an increased risk of blood cancers.

The team, from the Wellcome Sanger Institute, Calico Life Sciences, and the University of Cambridge, analyzed genetic sequencing data from over 200,000 individuals in the UK Biobank cohort. They searched for genes exhibiting signs of "positive selection," where mutations enable mutant cell populations to expand rapidly over time.

The 17 newly discovered genes were found to have similar disease associations as previously identified clonal hematopoiesis mutations, underscoring their clinical relevance in driving the accumulation of mutant blood cell clones.

By uncovering these previously unrecognized genetic drivers, the study paves the way for further exploration of the molecular mechanisms underlying clonal hematopoiesis and its role in disease development. Additionally, it could lead to improved genetic testing methods for identifying risks of blood cancers and cardiovascular diseases.

The incorporation of mutations in these 17 newly identified genes increased the prevalence of clonal hematopoiesis by 18 percent in the UK Biobank cohort, highlighting their significant impact on aging.

“While existing genetic tests have been valuable for early disease detection, our findings suggest there are opportunities to improve them further. 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,” explained Michael Spencer Chapman, co-first author of the study.