Figure 3.

Model of clonal hematopoiesis in normal and inflammatory conditions. In a normal person, hematopoietic stem cells (HSCs) will differentiate and self-renew over the course of a lifetime to replenish the blood system. HSCs will acquire somatic mutations as a result of proliferative stress. Certain HSC mutant clones (i.e., Tet2, DNMT3A) will acquire a selective advantage over wild type (WT) HSCs, resulting in clonal hematopoiesis. However, in an inflammatory environment, normal HSCs are exhausted and have impaired fitness. HSCs will acquire somatic mutations and will likely have an accelerated selective advantage over the exhausted HSCs, resulting in an earlier onset of CHIP (not illustrated in figure) and possibly in hematologic malignancy.