Abstract
Despite the significant progress that has been made in understanding the biology of leukemia stem cells (LSCs), some key questions regarding the concept of LSCs have not as yet been satisfactorily addressed experimentally. As a result, the clinical relevance of LSCs remains less than clear due to controversies caused largely by technical limitations in efficiently identifying LSCs. This has impeded our ability to fully address the features of genetic heterogeneity and metabolic/epigenetic plasticity of pre-LSCs and LSCs. With the development and use of humanized immunocompromised mice, we are able to more precisely analyze LSCs for their functions and interaction with the bone marrow niche. In addition, some promising targets in LSCs have recently been identified, including Sonic Hedgehog (SHH) and BCL-2, which are highly expressed in AML cells. It is hopeful that new anti-LSC compounds will be tested fully in clinical trials for their efficacy in treating human leukemias.