Identification and characterization of leukemia stem cells in murine MLL-AF9 acute myeloid leukemia.

Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA.
Cancer Cell (Impact Factor: 23.89). 11/2006; 10(4):257-68. DOI: 10.1016/j.ccr.2006.08.020
Source: PubMed

ABSTRACT Using a mouse model of human acute myeloid leukemia (AML) induced by the MLL-AF9 oncogene, we demonstrate that colony-forming cells (CFCs) in the bone marrow and spleen of leukemic mice are also leukemia stem cells (LSCs). These self-renewing cells (1) are frequent, accounting for 25%-30% of myeloid lineage cells at late-stage disease; (2) generate a phenotypic, morphologic, and functional leukemia cell hierarchy; (3) express mature myeloid lineage-specific antigens; and (4) exhibit altered microenvironmental interactions by comparison with the oncogene-immortalized CFCs that initiated the disease. Therefore, the LSCs responsible for sustaining, expanding, and regenerating MLL-AF9 AML are downstream myeloid lineage cells, which have acquired an aberrant Hox-associated self-renewal program as well as other biologic features of hematopoietic stem cells.

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