Clonal evolution in leukemia: preleukemia, evolutionary models, and clinical implications

Leukemia is a polyclonal and progressive disease with drastic intra-clone heterogeneity. During the early stages of disease development, it is mostly shaped by the deterministic effects of key initiating events, which could establish the roles of genomic instability and cell plasticity in clonal evolution. Later, preleukemic cells acquire successive genetic mutations, undergoing distinct evolutionary trajectories. In this review, we summarize the current understanding of how genetic lesions define distinct clonal architectures. We further highlight two classical evolutionary models and their relevant prognostic implications. Given that drug selection pressure remains a major driving force of relapse, we also discuss recurrent patterns of clonal evolution under chemotherapy and targeted therapy. Understanding the rationale for directing distinct clonal evolution patterns will be instrumental in the development of different therapeutic strategies to prevent or overcome drug resistance and relapse during disease progression.