TET2

TET2 encodes an enzyme that strips a chemical tag called a methyl group off DNA, flipping silenced genes back into an active, readable state. Blood stem cells rely on this switch to balance self-renewal against differentiation into mature immune cells. With age, a single blood stem cell that loses one working copy of TET2 can outcompete its neighbors and expand into a large clone, a state called clonal hematopoiesis. This condition affects roughly 10 percent of people over age 70 and roughly doubles the carrier's risk of cardiovascular disease. TET2-mutant immune cells drive that risk partly by overactivating the NLRP3 inflammasome, an inflammatory alarm system inside macrophages. The same mutant clones are also one of the most common first steps toward blood cancers such as myelodysplastic syndrome and acute myeloid leukemia. A single mutation, invisible on a normal blood count, therefore links aging blood to both heart disease and cancer.