Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Keynote Address
  • Published:

Keynote Address: Acute Leukemia Forum

The stem cell in the pathogenesis and treatment of myelogenous leukemia: a perspective

Leukemia volume 15, pages 1489–1494 (2001)Cite this article

Myelogenous leukemic hematopoiesis is monoclonal, but otherwise simulates normal hematopoiesis in that it is generated by a stem cell, and differentiation to progenitor cells and maturation to mature cells occur. Thus, the hierarchy of cells from stem to multipotential and monopotential progenitors and their maturation to precursors and mature cells mimics normal hematopoiesis. The execution of these genetic programs, however, ranges from closely simulating normal to bizarrely and unpredictably anarchic and dysfunctional. Moreover disturbances in anchoring relationships of cells to stroma and insufficient or exaggerated expression of cell death programs adds to the variety of malignant phenotypes. In this report, the evidence for the nature of leukemic hematopoiesis and the critical interplay between leukemic and normal hematopoiesis is reviewed from a historical perspective. A future focus on (1) the chemistry underlying the mechanisms of leukemic inhibition of normal hematopoiesis; (2) potential mechanisms to impair leukemic stem cell funtion; and (3) enhancement of normal stem cell function, so as to tip the balance in favor of the latter may provide needed new approaches to therapy.

Tissues that have a high rate of mature cell turnover must be organized in a hierarchy of cells with tight control over the processes of, first, stem cell self-renewal and differentiation and second, proliferation and maturation of progenitor cells, in order to meet the demands of programmed cell death or pathological consumption of mature cells. Hematopoiesis is particularly complex since ten unique basic lineages are derived from marrow parenchyma.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

References

  1. Maximow A . Der lymphozyt als gemeinsame Stammzelle der verschieden Blutelemente in der embryonalen Entwicklung und postfetalen Leben der Säugetiere Folia Haematologica (Leipzig) 1909 8: 125–141

    Google Scholar 

  2. Goodman JW, Hodgson GS . Evidence for stem cells in the peripheral blood of mice Blood 1962 19: 702–714

    CAS  PubMed  Google Scholar 

  3. Danchakoff V . Origin of blood cells. Development of the haematopoitic organs and regeneration of the blood cells from the standpoint of the monophyletic school Anatomical Record 1916 10: 397–414

    Article  Google Scholar 

  4. Kracke RR . Diseases of the Blood and Atlas of Hematology 2nd edn J.B. Lippincott Company: Philadelphia 1941

    Google Scholar 

  5. Lichtman MA (ed.) . Commentary on stem cell transplantation In Hematology: Landmark Papers of the Twentieth Century Academic Press: San Diego 2000 pp 669–670 and 715–717

    Chapter  Google Scholar 

  6. Till JE, McCulloch EA . A direct measurement of the radiosensitivity of normal mouse bone marrow cells Radiat Res 1961 14: 213–222

    Article  CAS  Google Scholar 

  7. Lichtman MA, Liesveld JN . Acute myelogenous leukemia In: Beutler E, Lichtman MA, Coller BS, Kipps TJ, Seligsohn U (eds) Williams Hematology 6th edn McGraw-Hill Book Company: New York 2001 pp 1047–1083

    Google Scholar 

  8. Linder D, Gartler SM . Glucose-6-phospate dehydrogenase mosaicism: utilization as a cell marker in studies of leiomyomas Science 1965 150: 67–69

    Article  CAS  Google Scholar 

  9. Lichtman MA, Liesveld JL . Chronic myelogenous leukemia and related disorders (section on Pathogenesis; origin from a stem cell clone, p 1086) In Williams Hematology 6th edn McGraw-Hill Book Company: New York 2001 pp 1085–1123

    Google Scholar 

  10. Lichtman MA . Classification and clinical manifestations of the clonal myeloid disorders In: Beutler E, Lichtman MA, Coller BS, Kipps TJ, Seligsohn U (eds) Williams Hematology 6th edn McGraw-Hill Book Company: New York 2001 pp 1019–1027

    Google Scholar 

  11. Lichtman, MA . Myelodysplasia or myeloneoplasia: thoughts on the nosology of clonal myeloid diseases Blood Cells, Mol Dis 2000 26: 572–581

    Article  CAS  Google Scholar 

  12. Turhan AG, Lemoine FM, Debert C, Bonnet ML, Baillou C, Picard F, Macintyre EA, Varet B . Highly purified primitive hematopoietic cells are PML-RARα negative and generate non-clonal progenitors in acute promyelocytic leukemia Blood 1995 85: 2154–2161

    CAS  PubMed  Google Scholar 

  13. Brendel C, Neubauer A . Characteristics and analysis of normal and leukemic stem cells.: current concepts and future directions Leukemia 2000 14: 1711–1717

    Article  CAS  Google Scholar 

  14. Feuring-Buske M, Hogge D . Hoechst 33342 efflux identifies a subpopulation of CD34+CD38− cells from patients with acute myelogenous leukemia (AML) which lack chromosomal abnormalities and are enriched for colony forming cells (CFC) and long-term culture initiating cells (LTC-IC) Blood 1999 94: (Suppl. 1) 656a (Abstr.)

    Google Scholar 

  15. Wulf GG, Wang R-Y, Kuehnle I, Weidner D, Marini F, Brenner MK, Andreef M, Goodell MA . Leukemic involvement of the CD34 negative bone marrow side population (SP) in patients with AML Blood 1999 94: (Suppl. 1) (Abstr.)

    Google Scholar 

  16. Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, Minden M, Paterson B, Caligiuri MA, Dick JE . A cell initiating human acute myeloid leukaemia after transplantation into SCID mice Nature 1994 367: 645–648

    Article  CAS  Google Scholar 

  17. Bonnet D, Dick JE . Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell Nature Med 1997 3: 730–737

    Article  CAS  Google Scholar 

  18. Furth J, Kahn MC . The transmission of leukemia in mice with a single cell Am J Cancer 1937 31: 276–282

    Google Scholar 

  19. Lichtman MA . Interrupting the inhibition of normal hematopoiesis in myelogenous leukemia: a hypothetical approach to therapy Stem Cells 2000 18: 304–306

    Article  CAS  Google Scholar 

  20. Kim SC, Yoo NC, Hahn JS, Lee S, Chong SY, Min YH, Ko YM . Monitoring of the WT-1 gene in peripheral blood of patients with acute leukemia by semiquantitative RT-PCR; possible marker for detection of minimal residual leukemia Yonsei Med 1997 38: 212–219

    Article  CAS  Google Scholar 

  21. Venditti A, Buccisano F, Del Poeta G, Maurillo L, Tamburini A, Cox, C, Battaglia A, Catalano G, Del Moro B, Cudillo L, Postorino M, Masi M, Amadori S . Level of minimal residual disease after consolidation therapy predicts outcome in acute myeloid leukemia Blood 2000 96: 3948–3952

    CAS  PubMed  Google Scholar 

  22. Orfao A, Vidriales B, López-Berges, MC, San Miguel JF . Immunophenotypic investigation of MRD in AML: technical approaches and clinical impact Proc 2nd Intl Conf Minimal Residual Dis 2001 p 37, (Abstr.)

  23. Russell NH . Biology of acute leukaemia Lancet 1997 349: 118–122

    Article  CAS  Google Scholar 

  24. Lichtman MA . Differentiation versus maturation of neoplastic hematopoietic cells: an important distinction Blood Cells Mol Dis 2001 27: 659–662

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine/Hematology-Oncology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 610, Rochester, NY 14642, USA

    MA Lichtman

Authors
  1. MA Lichtman
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

This paper is part of a series of keynote addresses to be published in Leukemia. They were presented at the Acute Leukemia Forum, San Francisco, 20 April 2001. Supported by an unrestricted educational grant from Immunex.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lichtman, M. The stem cell in the pathogenesis and treatment of myelogenous leukemia: a perspective. Leukemia 15, 1489–1494 (2001). https://doi.org/10.1038/sj.leu.2402247

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2402247

Keywords

This article is cited by

Search

Advanced search

Quick links