Putative mechanisms for AML stem cell and niche interactions in vivo. The bone marrow niche comprises endosteal (osteoblasts, osteoclasts, and acellular bone mineral matrix [osteopontin, calcium]) and perivascular components (comprising endothelial cells, CXCL-12 expressing adventitial reticular [CAR] cells, and MSCs). The niche provides support for self-renewal, quiescence, homing, engraftment, and proliferative potential for HSCs. LSCs may impair the function of the normal HSC niche by direct invasion or secretion of substances such as stem cell factor. LSCs can infiltrate these niches and may hijack these normal homeostatic processes, leading to enhanced self-renewal and proliferation, enforced quiescence, and resistance to chemotherapeutic agents. LSCs may also exhibit dysregulated homing and engraftment, leading to alternative niche formation.