CoChat
Sign Up
Cited by 5,864

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

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

Bonnet, Dominique, Dick, John E.·1997·Nature Medicine
DOI 10.1038/nm0797-730
Open this paper in CoChat — free account

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.

Overview

Integrity signals

Registry

Crossref · 10.1038/nm0797-730

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Show all 1 references

Research works printed but not linked: 38

  1. Fialkow, P. et al. Clonal development, stem-cell differentiation, and clinical remission in acute nonlymphocytic leukemia. N. Engl. J. Med. 317, 468–473 (1987). · DOI
  2. McCulloch, E. Stem cells in normal and leukemic hemopoiesis (Henry StrattonLecture). Blood 62, 1–13 (1983). · DOI
  3. Griffin, J. & Löwenberg, B. Clonogenic cells in acute myeloblastic leukemia. Blood 68, 1185–1195 (1986). · DOI
  4. Cline, M.J. The molecular basis of leukemia. N. Engl. J. Med. 330, 328–336 (1994). · DOI
  5. Berger, R. et al. Cytogenetic studies on 519 consecutive de novo acute nonlympho cytic leukemias. Cancer Genet. Cytogenet. 29, 9–21 (1987). · DOI
  6. Bennett, J. et al. Proposals for the classification of the acute leukemias. Br. J. Haematol. 33, 451–458 (1976). · DOI
  7. Fialkow, P.J. et al. Acute nonlymphocytic leukemia: Heterogeneity of stem cell origin. Blood 57, 1068–1073 (1981). · DOI
  8. Bartram, C.R. et al. Acute myeloid leukemia: Analysis of ras gene mutations and clonality defined by polymorphic X-linked loci. Leukemia 3, 247–256 (1989).
  9. van Lorn, K., Hagemeijer, A., Smit, E.M. & Lowenberg, B. In situ hybridization on May-Grünwald Giemsa-stained bone marrow and blood smears of patients with hematologic disorders allows detection of cell-lineage-specific cytogenetic abnormalities. Blood 82, 884–888 (1993). · DOI
  10. Fearon, E., Burke, P., Schiffer, C., Zehnbauer, B. & Vogelstein, B. Differentiation of leukemia cells to polymorphonuclear leukocytes in patients with acute nonlymphoblastic leukemia. N. Engl. J. Med. 315, 15–24 (1986). · DOI
  11. Feuring-Buske, M. et al. Trisomy 4 in ‘stem cell-like’ leukemic cells of a patient with AML. Leukemia 9, 1318–1320 (1995).
  12. Greaves, M.F. Stem cell origins of leukaemia and curability. Br. J. Cancer 67, 413–423 (1993). · DOI
  13. Keinänen, M., Griffin, J., Bloomfield, C., Machnrcki, J. & de la Chapelle, A. Clonalchromosomal abnormalities showing multiple-cell-lineage involvement in acute myeloid leukemia. N. Engl.J. Med. 318, 1153–1158 (1988). · DOI
  14. McCulloch, E.A. et al. Heterogeneity in acute myeloblastic leukemia. Leukemia 2, 38S–49S (1988).
  15. Haase, D. et al. Evidence for malignant transformation in acute myeloid leukemia at the level of early hematopoietic stem cells by cytogenetic analysis of CD34+sub-populations. Blood 86, 2906–2912 (1995). · DOI
  16. Mehrotra, B. et al. Cytogenetically aberrant cells in the stem cell compartment (CD34+1in−) in acute myeloid leukemia. Blood 86, 1139–1147 (1995).
  17. Larochelle, A. et al. Identification of primitive hematopoietic cells capable of repopulating NOD/SCID mouse bone marrow: Implications for gene therapy. Nature Med. 2, 1329–1337 (1996). · DOI
  18. Dick, J.E. Normal and leukemic stem cells assayed in SCID mice. Semin. Immunol. 8, 197–206 (1996). · DOI
  19. Bhatia, M., Wang, J., Kapp, U., Bonnet, D. & Dick, J. Purification of primitive human hematopoietic cells capable of repopulating NOD/SCID mice. Proc. Natl.Acad. Sci.USA 94, 5320–5325 (1997). · DOI
  20. Larochelle, A. et al. Engraftment of immune-deficient mice with primitivehematopoietic cells from beta-thalassemia and sickle cell anemia patients:Implications for evaluating human gene therapy protocols. Hum. Mol. Genet. 4, 163–172 (1995). · DOI
  21. Wang, J., Doedens, M. & Dick, J. Primitive human hematopoietic cells are enrichedin cord blood compared to adult bone marrow or mobilized peripheral blood as measured by the quantitative in vivo SCID-repopulating cell (SRC) assay. Blood 89, 3919–3924 (1997). · DOI
  22. Porter, E. & Berry, R. The efficient design of transplantable tumor assays. Br. J. Cancer 17, 583–595 (1964). · DOI
  23. Taswell, C. Limiting dilution assays for the determination of immunocompetent cell frequencies. I. Data analysis. J. Immunol. 126, 1614–1619 (1981). · DOI
  24. Civin, C. et al. Antigenic analysis of hematopoiesis. III. A hematopoietic progenitor cell surface antigen defined by a monoclonal antibody raised against KG-1 a cells. J. Immunol. 133, 157–165 (1984). · DOI
  25. Terstappen, L.W.W.M., Huang, S., Safford, M., Lansdorp, P.M. & Loken, M.R. Sequential generations of hematopoietic colonies derived from single nonlineagecommitted CD34+CD38 progenitor cells. Blood 77, 1218–1227 (1991). · DOI
  26. Terstappen, L. et al. Flow cytometry characterization of acute myeloid leukemia: IV. Comparison to the differentiation pathway of normal hematopoietic cells. Leukemia 6, 993–1000 (1992).
  27. Cashman, J. et al. Kinetic evidence of the regeneration of multilineage hematopoiesis from primitive cells in normal human bone marrow transplanted into immunodeficient mice. Stood (in the press).
  28. Moore, M., Williams, N. & Metcalfe, D. In vitro colony formation by normal and leukemic human hematopoietic cells: Characterization of the colony-forming cells. J. Natl. Cancer Inst. 50, 603 (1974). · DOI
  29. Sutherland, H., Blair, A. & Zapf, R.W. Characterization of a hierarchy in human acute myeloid leukemia progenitor cells. Blood 87, 4754–4761 (1996). · DOI
  30. Craig, W., Kay, R., Cutler, R.B. & Lansdorp, P.M. Expression of Thy-1 on human hematopoietic progenitor cells. J. Exp. Med. 177, 1331–1342 (1993). · DOI
  31. Terpstra, W. et al. Long-term leukemia-initiating capacity of a CD34− subpopulation of acute myeloid leukemia. Stood 87, 2187–2194 (1996).
  32. Sawyers, C., Gishizky, M., Quan, S., Golde, D. & Witte, O. Propagation of human blastic myeloid leukemias in the SCID mouse. Blood 79, 2089–2098 (1992). · DOI
  33. Cesano, A. et al. The severe combined immunodeficient (SCID) mouse as a model for myeloid leukemias. Oncogene 7, 827–836 (1992).
  34. Turhan, A.G. et al. Highly purified primitive hematopoietic stem cells are PML-RARA negative and generate nonclonal progenitors in acute promyelocytic leukemia. Stood 85, 2154–2161 (1995).
  35. Lapidot, T. et al. Cytokine stimulation of multilineage hematopoiesis from immature human cells engrafted in SCID mice. Science 255, 1137–1141 (1992). · DOI
  36. Vormoor, J. et al. Immature human cord blood progenitors engraft and proliferate to high levels in immune-deficient SCID mice. Stood 83, 2489–2497 (1994).
  37. Sirard, C. et al. Normal and leukemic SCID-repopulating cells (SRC) co-exist in the bone marrow and peripheral blood from CML patients in chronic phase while leukemic SRC are detected in blast crisis. Stood 87, 1539–1548 (1996).
  38. Waye, J.S. & Willard, H.F. Structure, organization and sequence of alpha satellite DNA from human chromosome 17: Evidence for evolution by unequal crossing-over and ancestral pentamer repeat shared with the human X chromosome. Mol. Cell. Biol. 6, 3156–3165 (1986). · DOI

Cited by

See all 5,864

Metadata

Authors
Bonnet, D., & Dick, J. E.
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
1997-07
Volume
3
Issue
7
Pages
730-737
ISSN
  • 1078-8956
  • 1546-170X
DOI
10.1038/nm0797-730
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.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. https://app.cochat.ai/papers/10.1038/nm0797-730
The paper
Bonnet, D., & Dick, J. E. (1997). Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nature Medicine. https://doi.org/10.1038/nm0797-730