Clonal Hematopoiesis and Its Impact on Human Health

Aging is associated with increased mutational burden in every tissue studied. Occasionally, fitness-increasing mutations will arise, leading to stem cell clonal expansion. This process occurs in several tissues but has been best studied in blood. Clonal hematopoiesis is associated with an increased risk of blood cancers, such as acute myeloid leukemia, which result if additional cooperating mutations occur. Surprisingly, it is also associated with an increased risk of nonmalignant diseases, such as atherosclerotic cardiovascular disease. This may be due to enhanced inflammation in mutated innate immune cells, which could be targeted clinically with anti-inflammatory drugs. Recent studies have uncovered other factors that predict poor outcomes in patients with clonal hematopoiesis, such as size of the mutant clone, mutated driver genes, and epigenetic aging. Though clonality is inevitable and largely a function of time, recent work has shown that inherited genetic variation can also influence this process. Clonal hematopoiesis provides a paradigm for understanding how age-related changes in tissue stem cell composition and function influence human health.

Automated summary

Aging is associated with increased mutational burden in all tissues. This can lead to stem cell clonal expansion, which is seen in various tissues but best studied in blood. Clonal hematopoiesis is linked to an increased risk of blood cancers and nonmalignant diseases like cardiovascular disease. Understanding clonal hematopoiesis can provide insights into age-related changes in stem cell composition and function.