Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell

@article{Bonnet1997HumanAM,
  title={Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell},
  author={Dominique Bonnet and John E. Dick},
  journal={Nature Medicine},
  year={1997},
  volume={3},
  pages={730-737}
}
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… Expand
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References

SHOWING 1-10 OF 41 REFERENCES
Characterization of a hierarchy in human acute myeloid leukemia progenitor cells.
TLDR
Results show that while heterogeneity exists between patients, it is possible to physically separate subpopulations of AML cells with different proliferative potentials and provides some support for the concept that quantitation of leukemic cells capable of producing CFU-blast for 4 weeks or more in vitro measures a less frequentLeukemic progenitor with higher proliferative Potential that may be the only relevant cell for maintaining the leukedmic clone in vivo. Expand
A cell initiating human acute myeloid leukaemia after transplantation into SCID mice
TLDR
This in vivo model replicates many aspects of human AML and defines a new leukaemia-initiating cell which is less mature than colony-forming cells. Expand
The severe combined immunodeficient (SCID) mouse as a model for human myeloid leukemias.
TLDR
Overall, these data indicate that the SCID mouse may represent a useful animal model for human myeloid leukemias and for the development of new pharmacological and molecular approaches to therapy. Expand
Long-term leukemia-initiating capacity of a CD34-subpopulation of acute myeloid leukemia.
TLDR
Both CD34- and CD34+ subsets of this AML sample contained immature progenitors with the capacity to initiate long-term AML growth as characterized in vivo (in SCID mice) as well as in vitro (in CAFC assay), indicating asynchrony between functional and immunophenotypical maturation of AML progenitor cell compartments. Expand
Evidence for malignant transformation in acute myeloid leukemia at the level of early hematopoietic stem cells by cytogenetic analysis of CD34+ subpopulations
TLDR
It is concluded that clonal karyotypic abnormalities are frequently found in the stem cell-like and more mature populations of patients with AML, irrespective of the phenotype of the bulk population of leukemic blasts and of the primary or secondary character of the leukemia. Expand
In vitro colony formation by normal and leukemic human hematopoietic cells: characterization of the colony-forming cells.
TLDR
Remission in both AML and CML was associated with a return to normal in the location, incidence, buoyant density, and suiciding index of colony-forming cells, suggesting density separation may make it possible to separate normal leukemic progenitor cells for therapeutic purposes. Expand
Clonal development, stem-cell differentiation, and clinical remissions in acute nonlymphocytic leukemia.
To determine whether acute nonlymphocytic leukemia develops clonally, to study the pattern of differentiation of the involved stem cells, and to determine whether clinical remissions are trueExpand
Normal and leukemic SCID-repopulating cells (SRC) coexist in the bone marrow and peripheral blood from CML patients in chronic phase, whereas leukemic SRC are detected in blast crisis.
TLDR
It is shown that irradiated severe combined immunodeficient mice can be transplanted with both normal and neoplastic cells from CML patients with either chronic or blast phase disease, and the feasibility of using this model for the future characterization of transplantable CML stem cells during disease progression is established. Expand
Propagation of human blastic myeloid leukemias in the SCID mouse.
TLDR
It is demonstrated that the SCID mouse is a reproducible system for the propagation of blastic human myeloid leukemias, and the differential growth of early- versus late-phase CML suggests that theSCID mouse may be a useful assay for identifying biologically aggressive leukedmias early in their clinical presentation. Expand
Clonogenic cells in acute myeloblastic leukemia.
TLDR
The identification, culture, growth characteristics, and biological and clinical significance of clonogenic cells in AML will be the subject of this review. Expand
...
1
2
3
4
5
...