Skip to main content
SpringerLink
Log in

Acute Nonlymphocytic Leukemia in Adults: Pathophysiology, Status of Current Therapy, and New Approaches

  • Conference paper
Acute Leukemias

Part of the book series: Haematology and Blood Transfusion / Hämatologie und Bluttransfusion ((HAEMATOLOGY,volume 30))

  • 115 Accesses

Abstract

Recent information concerning the cell biology of leukemias has provided new insights into the pathophysiology and pathogenesis of acute leukemia, involving the detection of leukemia viruses, oncogenes and their products, and the discovery of factors supporting clonal leukemic growth. Murine, avian, and cat leukemia viruses are well characterized. To date, only HTLV I appears to be a likely candidate as a human leukemia virus. For both avian and murine viruses, there is a fundamental classification distinction between long-latency viruses (LLV) and acute transforming viruses (ATV). The ATV are replication defective and must be propagated with a helper virus. They have within their genome an identifiable oncogene. The LLV do not contain such an oncogene and presumably act by “promotor insertion”, e.g., a retroviral long terminal repeat (LTR inserted 5’ to the cellular oncogene. Acutely appearing neoplasms are probably not clonal, but reflect infection of multiple target cells. Long-latency neoplasms, however, are clonal and probably reflect expansion of a random oncogenic event. There are usually differences between in vitro and in vivo target cell specificities for these viruses. Furthermore, pathogenicity in the animal is greatly affected by animal age, inoculum route, and the genetics of the recipients. Target cell specificities will hopefully be classified by new in vitro culture techniques for hematopoietic cells. Three avian ATV are interesting because of their apparent target cell specificity:

AEV (erythroblastosis virus), AMV (myeloblastosis virus), and MC 29 (myelocytomatosis virus). Relative numbers of target cells appear to differ for these viruses: 50 for AEV, 700 for AMV, and 3500 for MC 29. AEV (V-erb B) affects erythroid precursors (presumably BFU-E), AMV (Vmyb), early myeloid precursors, and MC 29 (V-myc), macrophage-like cells. In vitro AEV and MC 29, but not AMV, transform fibroblasts.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ymer S, Tucker WOJ, Sanderson CJ, Hapel AJ, Campbell HD, Young IG (1985) Constitutive synthesis of interleukin-3 by leukaemia cell line WEHI 3B is due to retroviral insertion near the gene. Nature 317: 255

    Article  PubMed  CAS  Google Scholar 

  2. Sherr CJ, Rettenmier CW, Sacca R, Roussel MF, Look AT, Stanley ER (1985) The c-fms prto- oncogene product is related to the receptor for the mono nuclear phagocyte growth factor, CSF-1. Cell 41: 665

    Article  PubMed  CAS  Google Scholar 

  3. Moore MAS, Williams N, Metcalf D (1973) In vitro colony formation by normal and leukemic human hematopoietic cells: characterization of the colony-forming cells. J Natl Cancer Inst 50: 603

    PubMed  CAS  Google Scholar 

  4. Löwenberg B, Swart K, Hagemeijer A (1980) PHA-induced colony formation in acute nonlymphocytic and chronic myeloid leukemia. Leuk Res 4: 143

    Article  PubMed  Google Scholar 

  5. Minden MD, Till JE, McCulloch EA (1978) Proliferative state of blast cell progenitors in acute myeloblastic leukemia ( AML ). Blood 52: 592

    Google Scholar 

  6. Griffin JD, Herrmann F, Wiper D, Sabbath KD (1986) Effects of recombinant GM-CSF on clonogenic cells in acute myeloid leukemia. Blood 66: 1448

    Google Scholar 

  7. Herrmann F, Oster W, Lindemann A, Ganser A, Dörken B, Knapp W, Griffin JD, Mertelsmann R (1986) Leukemic-colony-forming in acute myeloblastic leukemia: maturation, hierarchy, and growth conditions. In: Neth R, Gallo RC (eds) Modern trends in leukemia, Vol 7. Springer, Berlin Heidelberg New York Tokyo (to be published)

    Google Scholar 

  8. Herrmann F, Cannistra SA, Griffin JD (1986) T cell-monocyte interactions in the production of humoral factors regulating human granulopoieses in vitro. J Immunol 136: 2856

    PubMed  CAS  Google Scholar 

  9. Weinstein HJ, Mayer RJ, Rosenthal DS, Camitta BM, Coral FS, Nathan DG, FREI III E (1980) treatment of acute myelogenous leukemia in children and adults. N Engl J Med 303: 473

    Google Scholar 

  10. Vowels MR, White L, Hughes D (1985) Results of a pilot study for the treatment of childhood acute nonlymphoblastic leukemia. Cancer 55: 2337

    Article  PubMed  CAS  Google Scholar 

  11. Glucksberg H, Cheever MA, Farewell VT, Fefer A, Thomas ED (1983) Intensification therapy for acute non-lymphocyte leukemia in adults. Cancer 52: 198

    Article  PubMed  CAS  Google Scholar 

  12. Holmes R, Keating Mi, Cork A, Broach Y, Trujillo J., Dalton Jr, WT, McCredie KB, Freireich EJ (1985) A unique pattern of central nervous system leukemia in acute myelomyelomonocytic leukemia associated with inv(16) (p13q22). Blood 65: 1071

    PubMed  CAS  Google Scholar 

  13. Wolff SN, Marion J, Stein RS, Flexner JM, Lazarms HM, Spitzer TR, Phillips GL, Herzig RH, Herzig GP (1985) High-dose cytosine arabinoside and daunorubicin as consolidation therapy for acute nonlymphocytic leukemia in first remission: A pilot study. Blood 65: 1407

    Google Scholar 

  14. Brincker H (1985) Estimate of overall treatment results in acute nonlymphocytic leukemia based on age-specific rates of incidence and of complete remission. Cancer Treat Rep 69: 5

    PubMed  CAS  Google Scholar 

  15. Spriggs D, Griffin JD, Wisch J, Kufe D (1985) Clinical pharmacology of low-dose cytosine arabinoside. Blood 65: 1087

    PubMed  CAS  Google Scholar 

  16. Burnett AK, Watkins R, Maharaj D, McKinnon S, Tansey P, Alcorn M, Singer CRJ, McDonald GR, Robertson AG (1984) Transplantation of un-purged autologous bone marrow in acute myeloid leukemia in first remission. Lancet II: 1068

    Google Scholar 

  17. Löwenberg B, Hagenbeek A, Sizoo W, De Gast GC, Verdonck LF (1984) Bone marrow transplantation studies in acute leukaemia. Lancet 11: 1400

    Article  Google Scholar 

  18. Casellas P, Canat X, Fauser AA, Gros O, Laurent G, Poncelet P, Jansen FK (1985) Optimal elimination of leukemic T cells from human bone marrow with T 101-Ricin A-chain immunotoxin. Blood 65: 289

    PubMed  CAS  Google Scholar 

  19. De Fabritiis P. Bregni M, Lipton J, Greenberger J, Nadler L, Rothstein L, Körbling M, Ritz J, Bast RC (1985) Elimination of clono-genic Burkitt’s lymphoma cells from human bone marrow using 4-hydroperoxycyclophosphamide in combination with monoclonal antibodies and complement. Blood 65: 1064

    PubMed  Google Scholar 

  20. Uckun FM, Ramakrishnan S, Haag D, Houston LL (1985) Ex vivo elimination of lymphoblastic leukemia cells from human marrow by mafosfamid. Leuk Res 9: 83

    Article  PubMed  CAS  Google Scholar 

  21. Kaizer H, Stuart RK, Brookmeyer R, Beschorner WE, Braine JG, Burns WH, Fuller DJ, Körbling M, Mangan KF, Saral R, Sensenbrenner L, Shadduck RK, Shende AC, Tutschka P, Yeager AM, Zinkham WH, Colvin OM, Santos GW (1985) Autologous bone marrow transplantation in acute leukemia: a phase I study of in vitro treatment of marrow with 4-hydroperoxycyclophosphamide to purge tumor cells. Blood 65: 1504

    PubMed  CAS  Google Scholar 

  22. Bos JL, Toksoz D, Marshall CJ, Verlaan-De Vries M, Veenemann GH, Van Der Erb AJ, Van Boom JH, Janssen JWG, Steenvoorden ACM (1985) Amino-acid substitutions at codon 13 of the N-ras oncogene in human acute myeloid leukaemia. Nature 315: 726

    Article  PubMed  CAS  Google Scholar 

  23. Hapel AJ, Fung MC, Johnson RM, Young IG, Johnson G, Metcalf D (1985) Biological properties of molecularly cloned and expressed murine interleukin-3. Blood 65: 1453

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Hematology, Johannes Gutenberg-University, Mainz, Federal Republic of Germany

    F. Herrmann

Authors
  1. R. H. Mertelsmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. Herrmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Departments of Internal Medicine and Pediatrics, University of Münster, Albert-Schweitzer-Strasse 33, D-4400, Münster, Federal Republic of Germany

    T. Büchner , G. Schellong , W. Hiddemann , D. Urbanitz  & J. Ritter , , ,  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1987 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Mertelsmann, R.H., Herrmann, F. (1987). Acute Nonlymphocytic Leukemia in Adults: Pathophysiology, Status of Current Therapy, and New Approaches. In: Büchner, T., Schellong, G., Hiddemann, W., Urbanitz, D., Ritter, J. (eds) Acute Leukemias. Haematology and Blood Transfusion / Hämatologie und Bluttransfusion, vol 30. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-71213-5_2

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-71213-5_2

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-16556-9

  • Online ISBN: 978-3-642-71213-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation