Letter | Published:

A cell initiating human acute myeloid leukaemia after transplantation into SCID mice

Nature volume 367, pages 645648 (17 February 1994) | Download Citation

Subjects

Abstract

MOST human acute myeloid leukaemia (AML) cells have limited proliferative capacity, suggesting that the leukaemic clone may be maintained by a rare population of stem cells1–5. This putative leukaemic stem cell has not been characterized because the available in vitro assays can only detect progenitors with limited proliferative and replating potential4–7. We have now identified an AML-initiating cell by transplantation into severe combined immune-deficient (SCID) mice. These cells homed to the bone marrow and proliferated extensively in response to in vivo cytokine treatment, resulting in a pattern of dissemination and leukaemic cell morphology similar to that seen in the original patients. Limiting dilution analysis showed that the frequency of these leukaemia-initiating cells in the peripheral blood of AML patients was one engraftment unit in 250,000 cells. We fractionated AML cells on the basis of cell-surface-marker expression and found that the leukaemia-initiating cells that could engraft SCID mice to produce large numbers of colony-forming progenitors were CD34+CD38; however, the CD34+CD38+ and CD34 fractions contained no cells with these properties. 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.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    , & Cell 64, 337–350 (1991).

  2. 2.

    , , , & New Engl. J. Med. 315, 15–24 (1986).

  3. 3.

    , , , & New Engl. J. Meet. 318 1153–1158 (1988).

  4. 4.

    & Blood 68, 1185–1195 (1986).

  5. 5.

    & in Hematology of Infancy and Childhood (eds Nathan, D. G. & Oski, F. A.) 1288–1318 (Saunders, Philadelphia, 1993).

  6. 6.

    , , & J. cell. Physiol. Suppl. 1, 103–111 (1982).

  7. 7.

    & Blood 81, 281–292 (1993).

  8. 8.

    & Science 242, 1706–1709 (1988).

  9. 9.

    et al. Science 255, 1137–1141 (1992).

  10. 10.

    et al. Science 246, 1597–1600 (1991).

  11. 11.

    et al. Blood 78, 2973–2981 (1991).

  12. 12.

    , & Immun. Rev. 124, 25–43 (1991).

  13. 13.

    et al. Oncogene 7, 827–836 (1992).

  14. 14.

    , , , & Blood 79, 2089–2098 (1992).

  15. 15.

    et al. Expl Hemat. 19, 991–993 (1991).

  16. 16.

    et al. J. Immun. 133, 157–165 (1984).

  17. 17.

    et al. Leukemia 6, 993–1000 (1992).

  18. 18.

    , , , & Blood 77, 1218–1227 (1991).

  19. 19.

    , , , & J. clin. Invest. 75, 961–969 (1985).

  20. 20.

    et al. Blut 61, 267–270 (1990).

  21. 21.

    , & Meth. molec. cell. Biol. 2, 17–25 (1990).

  22. 22.

    et al. Br. J. Haemal 33, 451–458 (1976).

  23. 23.

    & Molec. cell. Biol. 6, 3156–3165 (1986).

  24. 24.

    & Brit. J. Cancer 17, 583–595 (1964).

Download references

Author information

Author notes

    • Trang Hoang
    •  & Julio Caceres-Cortes

    Clinical Research Institute, Montreal, Quebec H2W 1R7, Canada

    • Mark Minden

    Department of Medicine, Princess Margaret Hospital, Toronto, Ontario M4X 1K9, Canada

    • Bruce Paterson

    Department of Oncologic Pathology, Princess Margaret Hospital, Toronto, Ontario M4X 1K9, Canada

    • Michael A. Caligiuri

    Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York 14263-0001, USA

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 M5G 1X8, Canada

    • Tsvee Lapidot
    • , Christian Sirard
    • , Josef Vormoor
    • , Barbara Murdoch
    • , Trang Hoang
    • , Julio Caceres-Cortes
    • , Mark Minden
    • , Bruce Paterson
    • , Michael A. Caligiuri
    •  & John E. Dick

Authors

  1. Search for Tsvee Lapidot in:

  2. Search for Christian Sirard in:

  3. Search for Josef Vormoor in:

  4. Search for Barbara Murdoch in:

  5. Search for Trang Hoang in:

  6. Search for Julio Caceres-Cortes in:

  7. Search for Mark Minden in:

  8. Search for Bruce Paterson in:

  9. Search for Michael A. Caligiuri in:

  10. Search for John E. Dick in:

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/367645a0

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.