Leukemia stem cells in acute myeloid leukemia

Recently, many malignancies have been demonstrated to be modeled on a loose developmental hierarchy. At the apex of these hierarchies sit so-called cancer stem cells or cancer-initiating cells, which are wholly responsible for the continued growth and propagation of the tumor. The first such cancer stem cells were described in acute myeloid leukemia (AML). The discovery of these cells also has important clinical implications. Following treatment, the majority of tumors, including leukemias, initially respond. However, relapse is common and often fatal. A likely explanation for this is that leukemia stem cells are relatively insensitive to current therapies and that tumor bulk reduction reflects the death of leukemic blasts that lack tumor initiation potential. This review will focus on what is known of the molecular and cellular biology of the leukemia stem cell and the leukemia stem cell niche in AML and then will identify molecular pathways critical for leukemia stem cells. Finally, we will identify current and prospective therapeutic targets to facilitate eradication of leukemia stem cells. It is hoped that, in defining the biology of cancer stem cells and how they differ from their adult tissue stem cell counterpart, we should identify therapeutic targets to improve treatment outcomes in leukemia and other malignant diseases.