As tissues age, they quietly accumulate many mutations that can drive cancer. In the hematopoietic system, such mutations often appear in otherwise healthy individuals as clonal hematopoiesis (CH), a process in which certain blood stem cell (HSC) clones gain a growth advantage over non-mutated clones, allowing them to expand steadily over time. A condition known as CHIP (clonal hematopoiesis of indeterminate potential) is associated with an increased risk of blood cancers as well as other chronic illnesses, including heart disease. However, not all those with CHIP develop disease, and some mutant stem cell clones remain stable or even diminish over time, suggesting that inherited and/or environmental factors can restrain or slow CH. Now, a newly identified and rare genetic variant has been identified that slows the growth of mutated blood stem cells and reduces the risk of leukemia. The findings offer insight into why some people are naturally more resistant to clonal expansion and age-related blood cancers despite acquiring risky mutations. This work is published in Science in the paper, “Inherited resilience to clonal hematopoiesis by modifying stem cell RNA regulation.” To gain further insight into this process, the lab of Vijay G. Sankaran, MD, PhD, at Harvard Medical School performed a GWAS meta-analysis on data from more than 640,000 individuals to search for inherited DNA variants that protect against CH. The team identified a noncoding regulatory variant, rs17834140-T, that substantially lowers the risk of CHIP and reduces the likelihood of developing blood cancers. “The ability to predict disease risk…
