Clonal Hematopoiesis, Inflammation, and Hematologic Malignancy
- Annu Rev Pathol. 2024 Jan 24:19:479-506. doi: 10.1146/annurev-pathmechdis-051222-122724.
- 1. Department of Hematopathology and Molecular Diagnostics, Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
- 2. Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, New York, USA.
- 3. Department of Medicine, New York University Grossman School of Medicine, New York, New York, USA.
- 4. Hematology Section, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA; email: [email protected].
- 5. Myeloid Malignancies Program, National Institutes of Health, Bethesda, Maryland, USA.
Somatic or acquired mutations are postzygotic genetic variations that can occur within any tissue. These mutations accumulate during aging and have classically been linked to malignant processes. Tremendous advancements over the past years have led to a deeper understanding of the role of somatic mutations in benign and malignant age-related diseases. Here, we review the somatic mutations that accumulate in the blood and their connection to disease states, with a particular focus on inflammatory diseases and Myelodysplastic Syndrome. We include a definition of clonal hematopoiesis (CH) and an overview of the origins and implications of these mutations. In addition, we emphasize somatic disorders with overlapping inflammation and hematologic disease beyond CH, including paroxysmal nocturnal hemoglobinuria and aplastic anemia, focusing on VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. Finally, we provide a practical view of the implications of somatic mutations in clinical hematology, pathology, and beyond.