Figure 3.

Clonal hematopoiesis. As we age, somatic mutations accumulate in bone marrow hematopoietic stem cells, some of which confer a competitive advantage or fitness, leading to clonal expansion of the mutated cells. Consequently, the bone marrow expels clonal descendants of the mutant stem cells into peripheral circulation. In this premalignant condition called clonal hematopoiesis, genes frequently mutated are Tet methylcytosine dioxygenase 2 (TET2), DNA methyltransferase 3 alpha (DNMT3A), addition of sex combs like 1 (ASXL1), and Janus kinase 2 (JAK2), and the somatic mutations confer both increased proliferation capacity and inflammatory signature to the mutated cells, thereby leading to adverse post-infarction heart failure with enhanced inflammation.