Longevity & AgingInherited gene variant shields blood stem cells from age-related clonal expansion
As we age, blood stem cells acquire mutations that can expand into clones, a condition called clonal hematopoiesis (CH) that raises the risk of blood cancers and other chronic diseases. Using a meta-analysis of 43,619 CHIP carriers and 598,761 controls, researchers found a common variant, rs17834140-T, at chromosome 17q22 that is the most protective CHIP variant identified. It weakens a GATA2-bound enhancer and selectively lowers the RNA-binding protein MSI2 in blood stem cells. This reduces stem cell self-renewal and fitness, slows clone growth over time, and blunts the advantage of ASXL1 mutations. Carriers also had lower risk of myeloid malignancies. The findings suggest that inhibiting MSI2 or its targets could be a strategy for blood cancer prevention.
