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Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell
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.
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“Mouse xenograft models have shown that leukemic cells have a phenotypic hierarchy, and that only a subpopulation of malignant cells is able to recapitulate the disease in recipient animals [10,11].”
From Mitochondrial Dysfunction in Human Leukemic Stem/Progenitor Cells upon Loss of RAC2 (2015) · cites this paper as [10]
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Metadata
- Authors
- Bonnet, D., & Dick, J. E.
- Venue
- Nature Medicine
- Published
- 1997-07
- Volume
- 3
- Issue
- 7
- Pages
- 730-737
- ISSN
- 1078-8956
- 1546-170X
- Cited by
- 5,864
- References
- 1
- Language
- en
- Licence
- www.springer.com/tdm (tdm)
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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