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Leukemia Stem Cells and Microenvironment: Biology and Therapeutic Targeting

2011; Lippincott Williams & Wilkins; Volume: 29; Issue: 5 Linguagem: Inglês

10.1200/jco.2010.31.0904

1527-7755

Marina Konopleva, Craig T. Jordan,

Hematopoietic Stem Cell Transplantation

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.