Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis

作者：Serine Avagyan, Jonathan E. Henninger, William Mannherz, Meeta Mistry, Joon Yoon, Song Yang, M. Weber, Jessica L. Moore, Leonard I. Zon · 发表于：Science · 年份：2021 · DOI：10.1126/science.aba9304 · 被引用次数：201 · 研究领域：Acute Myeloid Leukemia Research、Single-cell and spatial transcriptomics、Zebrafish Biomedical Research Applications

Colorful clones in the blood Stem cells in regenerating tissues such as the blood can acquire mutations that enable a growth advantage, increasing the chance of developing cancer. It is unclear how such diverse mutations promote clonal fitness. Avagyan et al . generated a platform in zebrafish to label clones with unique hues while inducing mutations in genes implicated in human blood disorders. Mutations in some genes caused clones to expand over time, resulting in clonal dominance. Progenitors in the dominant clone expressed anti-inflammatory factors to resist the inflammatory environment produced by their own mature progeny, leading to a self-perpetuating cycle promoting clonal fitness. Targeting these resistance pathways may be used to abate clonal hematopoiesis and prevent its associated pathology. —BAP