Clinical progression of clonal hematopoiesis is determined by a combination of mutation timing, fitness, and clonal structure.

ABSTRACT: Clonal hematopoiesis (CH) is characterized by expanding blood cell clones carrying somatic mutations in healthy aged individuals and is associated with various age-related diseases and all-cause mortality. While CH mutations affect diverse genes associated with myeloid malignancies, their mechanisms of expansion and disease associations remain poorly understood. We investigate the relationship between clonal fitness and clinical outcomes by integrating data from three longitudinal aging cohorts (n=713, observations=2,341). We demonstrate pathway-specific fitness advantage and clonal composition influence clonal dynamics. Further, the timing of mutation acquisition is necessary to determine the extent of clonal expansion reached during the host individual's lifetime. We introduce MACS120, a

SUBMITTER: Latorre-Crespo E 

PROVIDER: S-EPMC11908133 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature