TY - JOUR
T1 - Clonal Hematopoiesis, Inflammation, and Hematologic Malignancy
AU - Kanagal-Shamanna, Rashmi
AU - Beck, David B.
AU - Calvo, Katherine R.
N1 - Publisher Copyright:
© 2024 Annual Reviews Inc.. All rights reserved.
PY - 2024/1/24
Y1 - 2024/1/24
N2 - 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.
AB - 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.
KW - MDS
KW - UBA1
KW - VEXAS
KW - autoimmune
KW - clonal hematopoiesis
KW - inflammation
KW - myelodysplastic syndrome
KW - plasma cell neoplasm
UR - http://www.scopus.com/inward/record.url?scp=85183472501&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85183472501&partnerID=8YFLogxK
U2 - 10.1146/annurev-pathmechdis-051222-122724
DO - 10.1146/annurev-pathmechdis-051222-122724
M3 - Review article
C2 - 37832948
AN - SCOPUS:85183472501
SN - 1553-4006
VL - 19
SP - 479
EP - 506
JO - Annual Review of Pathology: Mechanisms of Disease
JF - Annual Review of Pathology: Mechanisms of Disease
ER -