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Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell
Author(s): Bonnet D, Dick JE
Source: NATURE MEDICINE    Volume: 3    Issue: 7    Pages: 730-737    Published: JUL 1997  
Times Cited: 1,185     References: 38     
Abstract: On the subject of acute myeloid leukemia (AML), there is little consensus about the target cell within the hematopoietic stem cell hierarchy that is susceptible to leukemic transformation, or about the mechanism that underlies the phenotypic, genotypic and clinical heterogeneity. Here we demonstrate that the cell capable of initiating human AML in non-obese diabetic mice with severe combined immunodeficiency disease (NOD/SCID mice)-termed the SCID leukemia-initiating cell, or SL-IC-possesses the differentiative and proliferative capacities and the potential for self-renewal expected of a leukemic stem cell. The SL-ICs from all subtypes of AML analyzed, regardless of the heterogeneity in maturation characteristics of the leukemic blasts, were exclusively CD34(++) CD38(-), similar to the cell-surface phenotype of normal SCID-repopulating cells, suggesting that normal primitive cells, rather than committed progenitor cells, are the target for leukemic transformation. The SL-ICs were able to differentiate in vivo into leukemic blasts, indicating that the leukemic clone is organized as a hierarchy.
Document Type: Article
Language: English
Reprint Address: Bonnet, D (reprint author), HOSP SICK CHILDREN, RES INST, DEPT GENET, 555 UNIV AVE, TORONTO, ON M5G 1X8 CANADA
Addresses:
1. UNIV TORONTO, DEPT MOL & MED GENET, TORONTO, ON M5G 1X8 CANADA
Publisher: NATURE PUBLISHING CO, 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707
Subject Category: Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental
IDS Number: XG767
ISSN: 1078-8956
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