Emergency hematopoiesis in sepsis: A pathway to myeloid clonal expansion

Abstract

Clonal hematopoiesis of indeterminate potential (CHIP) arises from somatic mutations in hematopoietic stem cells (HSCs) that confer a fitness advantage and is associated with increased risks of myeloid neoplasia, cardiovascular disease, and mortality. 1 – 5 Although aging is a major determinant of CHIP, the contributions of other factors, including environmental exposures, chemotherapy, and immune perturbations, remain incompletely defined. 6 – 9 Aging increases susceptibility to both sepsis and CHIP, and common CHIP ‐ associated mutations alter HSC function and immune responses, potentially influencing infection severity. 10,11 During severe infections such as sepsis, rapid hematopoietic expansion manifests as emergency hematopoiesis (EH), a process increasingly linked to clonal hematopoiesis (CH). 12 – 14 We therefore examined sepsis as a clinical framework in which EH interacts with CH by determining the CH prevalence in adults