Figure 4.

Fitness landscapes are themselves dynamic and can change in the context of a healthy versus aberrant microenvironment. In the healthy microenvironmental context (left), the nonmutated, wild-type clone exhibits the greatest fitness advantage as compared with TP53-mutated clones with mono- and biallelic loss-of-function mutations. The endogenous bone marrow microenvironment favors wild-type clones as an evolutionary mechanism to maintain intact hematopoiesis, a feature essential for viable life during reproductive years. In contrast, an anemic microenvironment (right) may sustain aberrant growth signals in an effort to boost erythropoiesis, perhaps providing a selective advantage to the more proliferative TP53-mutated clones. WT, wild-type.