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Link to original content: https://doi.org/10.1038/nm0797-730
Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell | Nature Medicine
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Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell

Nature Medicine volume 3, pages 730–737 (1997)Cite this article

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 differentiate 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.

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Author notes

  1. John E. Dick: Correspondence should be addressed to J.E.D.

Authors and Affiliations

  1. Department of Genetics, Research Institute, Hospital for Sick Children and Department of Molecular and Medical Genetics, University of Toronto, 555 University Avenue, Toronto, Ontario, M5G1X8, Canada

    Dominique Bonnet & John E. Dick

  2. Department of Genetics, Research Institute, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada, M5G 1X8

    John E. Dick

Authors
  1. Dominique Bonnet
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  2. John E. Dick
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Bonnet, D., Dick, J. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3, 730–737 (1997). https://doi.org/10.1038/nm0797-730

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