Acute myeloid leukemia stem cells

Abstract

For more than two decades, the leukemia stem cell (LSC) model has received considerable attention following the identification of rare engrafting cell subpopulations in patient-derived xenograft assays. LSCs are thought to induce leukemogenesis and recurrence and are considered excellent targets in the development of curative therapies. Experimental support for this model in human malignancy was first achieved for acute myeloid leukemia (AML). Subsequent studies of AML stem cells have revealed a dormant state and enrichment of the CD34⁺CD38^- subpopulation. These cells express specific antigens (e.g., CD123, CD47, TIM-3) and depend on several signaling pathways (e.g., WNT/β-catenin and PI3K/AKT/FOXO pathways) and mitochondrial respiration for growth and survival. More recently, genetic and immunological studies revealed that LSCs are genetically heterogenous and can escape host antitumor immunity. This article summarizes the current knowledge about LSCs and discusses future challenges involving the translation of research findings into real-time benefits for AML patients.