Recent studies, mostly using genetic models of CH in mice, started to shed light on this question and suggest that complex context-dependent but interrelated mechanisms affect HSC survival, proliferation, differentiation, and self-renewal to improve fitness in Asxl1 (Figure 5), Dnmt3a (Figure 6), and Tet2 mutants (Figure 7) [45]. This evidence concerns the gene DNMT3A and cyclic hematopoiesis.