2022/11/30 by Herra Ahmad, Nikolaus Jahn, Siddhartha Jaiswal · 64 citations
Biochemistry, Genetics and Molecular Biology · Medicine · #Acute Myeloid Leukemia Research #Biology #Disease #Epigenetics #Epigenetics and DNA Methylation #Gene #Genetics #Haematopoiesis #Hematopoietic stem cell #Immune system #Immunology #Inflammation #Internal medicine #Medicine #Myeloid #Myeloid leukemia #Myeloproliferative Neoplasms: Diagnosis and Treatment #Somatic evolution in cancer #Stem cell #clone (Java method)
paper · pdf · doi:10.1146/annurev-med-042921-112347
published in Annual Review of Medicine 74(1), 249-260 (Annual Reviews)
openalex publication_date 2022/11/30 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/25
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.