{"title":"克隆造血及其对人类健康的影响。","authors":"Herra Ahmad, Nikolaus Jahn, Siddhartha Jaiswal","doi":"10.1146/annurev-med-042921-112347","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":8056,"journal":{"name":"Annual review of medicine","volume":"74 ","pages":"249-260"},"PeriodicalIF":15.1000,"publicationDate":"2023-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"11","resultStr":"{\"title\":\"Clonal Hematopoiesis and Its Impact on Human Health.\",\"authors\":\"Herra Ahmad, Nikolaus Jahn, Siddhartha Jaiswal\",\"doi\":\"10.1146/annurev-med-042921-112347\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":8056,\"journal\":{\"name\":\"Annual review of medicine\",\"volume\":\"74 \",\"pages\":\"249-260\"},\"PeriodicalIF\":15.1000,\"publicationDate\":\"2023-01-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"11\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annual review of medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1146/annurev-med-042921-112347\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annual review of medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1146/annurev-med-042921-112347","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
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.
期刊介绍:
The Annual Review of Medicine, which has been published since 1950, focuses on important advancements in diverse areas of medicine. These include AIDS/HIV, cardiology, clinical pharmacology, dermatology, endocrinology/metabolism, gastroenterology, genetics, immunology, infectious disease, neurology, oncology/hematology, pediatrics, psychiatry, pulmonology, reproductive medicine, and surgery. The journal's current volume has transitioned from a gated access model to an open access model through the Annual Reviews' Subscribe to Open program. All articles published in the journal are now available under a CC BY license.