The eco-evolutionary dynamics of acute myeloid leukemia: From clonal games to clinical intervention

Acute myeloid leukemia (AML) is a hematologic malignancy characterized by high clonal heterogeneity, whose initiation and progression are driven by a complex process of clonal evolution. Integrating recent research advances, this review summarizes the multidimensional features of clonal evolution in AML, including the origin and heterogeneity of clones, the interaction between clones and the bone marrow microenvironment, the genetic mutation profiles of AML clones, the dynamic patterns of clonal evolution, as well as the intrinsic and extrinsic drivers that fuel this process-such as genomic instability, environmental selection pressure, the Dykhuizen-Hartl effect, the Baldwin effect, and interclonal game dynamics. Furthermore, this article discusses the clinical implications of clonal evolution in AML prognosis assessment, relapse mechanisms, and therapeutic strategies, with particular emphasis on the pivotal role of single‑cell multi‑omics technologies in this field. Understanding the principles of clonal evolution in AML will help elucidate the mechanisms of disease progression, refine risk stratification, and provide novel insights for developing combination therapies that target both the clonal architecture and the microenvironment.