title: Leukemia stem cells and microenvironment: biology and therapeutic targeting.
abstract: Acute myelogenous leukemia is propagated by a subpopulation of leukemia stem cells (LSCs). In this article, we review both the intrinsic and extrinsic components that are known to influence the survival of human LSCs. The intrinsic factors encompass regulators of cell cycle and prosurvival pathways (such as nuclear factor kappa B [NF-κB], AKT), pathways regulating oxidative stress, and specific molecular components promoting self-renewal. The extrinsic components are generated by the bone marrow microenvironment and include chemokine receptors (CXCR4), adhesion molecules (VLA-4 and CD44), and hypoxia-related proteins. New strategies that exploit potentially unique properties of the LSCs and their microenvironment are discussed.
authors.affiliation: The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 428, Houston, TX 77030, USA. mkonople@mdanderson.org
authors.forename: Marina Y
authors.initials: MY
authors.lastname: Konopleva
authors.forename: Craig T
authors.initials: CT
authors.lastname: Jordan
mesh_terms: D000818:Animals; D002470:Cell Survival; D054377:Chemokine CXCL12 / Q000502:physiology; D019008:Drug Resistance, Neoplasm; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology*
chemical_list: D054377:Chemokine CXCL12