Clonal hematopoiesis and nonhematologic disorders

Abstract

Clonal expansions of mutated hematopoietic cells, termed clonal hematopoiesis, are common in aging humans. One expected consequence of mutation-associated clonal hematopoiesis is an increased risk of hematologic cancers, which has now been shown in several studies. However, the hematopoietic stem cells that acquire these somatic mutations also give rise to mutated immune effector cells, such as monocytes, granulocytes, and lymphocytes. These effector cells can potentially influence many disease states, especially those with a chronic inflammatory component. Indeed, several studies have now shown that clonal hematopoiesis associates with increased risk of atherosclerotic cardiovascular disease. Emerging data also associate clonal hematopoiesis with other nonhematologic diseases. Here, we will review recent studies linking clonal hematopoiesis to altered immune function, inflammation, and nonmalignant diseases of aging.

Graphical abstract

Figure 1.

Ten most frequently mutated genes in CHIP. Data were obtained from Bick et al.

Figure 2.

Scaled density plots for VAF of CHIP-associated mutations. Targeted sequencing data were obtained from Abelson et al, whole-exome sequencing (WES) data were obtained from Jaiswal et al, and whole-genome sequencing (WGS) data were obtained from Bick et al. The dashed red line is drawn at variant allele fraction (VAF) 0.02, the cutoff for CHIP. The depth of coverage is the primary factor that determines the shape of the distribution for VAF.

Figure 3.

Summary of reported associations of CHIP with nonhematologic diseases.