Acute myeloid leukemia stem cells from genomic and immunological perspectives

Evidence of human leukemia stem cells (LSCs) in acute myeloid leukemia (AML) was first reported nearly a quarter century ago through the identification of rare engrafting cell subpopulations in patient-derived xenograft assays. Since then, studies have revealed diverse characteristics of AML stem cells. Initiating mutations convert normal hematopoietic stem cells (HSCs) to pre-leukemic HSCs. The repopulation advantage of pre-leukemic HSCs over normal HSCs leads to clonal evolution. Acquisition of additional mutations in pre-leukemic HSCs results in the development of AML composed of genetically distinct subclones. Each subclone contains LSCs with unique characteristics, and these LSCs contribute to therapeutic resistance and relapse. Interestingly, some LSCs can escape from antitumor immune responses, thereby survive the treatment. This article summarizes recent advances in the field of LSC biology from genomic and immunological perspectives.