Colony-Stimulating Factors (rhG-CSF, rhGM-CSF, rhIL-3, and BCFG) Recruit Myeloblastic and Lymphoblastic Leukemic Cells and Enhance the Cytotoxic Effects of Cytosine-Arabinoside

  • M. Andreeff
  • A. Tafuri
  • S. Hegewisch-Becker
Part of the Haematology and Blood Transfusion / Hämatologie und Bluttransfusion book series (HAEMATOLOGY, volume 33)

Abstract

The treatment of adult and pediatric acute lymphoblastic leukemia (ALL) and acute myeloblastic leukemia (AML) has resulted in long-term survival and cures in a substantial number of patients [1–3]. Best results have been achieved in pediatric ALL with approximately 70% of patients in ongoing long-term remission [4]. Results in patients with adult leukemias are much worse: though 60%–80% of patients with AML achieved complete remission, only 15% are alive after 5 years [1]. In adult ALL, the incidence of remission is ca. 80%–90%, but only 35% of these remain in long-term remission [1, 3, 5]. These results have not improved significantly over the last 15 years, despite efforts in many centers and in multicentric trials to test new drug schedules, drug combinations, and treatment modalities, including bone marrow transplantation [6]. Clearly, new approaches to improve survival of these potentially curable patients are needed.

Keywords

Leukemia Oncol Iodide Fluorescein Cytosine 

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References

  1. 1.
    Clarkson B, Gee T, Arlin Z et al. (1984) Current status of treatment of acute leukemia in adults: an overview. In: Buechner T (ed) Therapie der akuten Leukämien. Springer, Berlin Heidelberg New York, pp 1–31CrossRefGoogle Scholar
  2. 2.
    Berman E, Raymond V, Gee T et al. (1989) Idarubicin in acute leukemia: results of studies at Memorial Sloan-Kettering Cancer Center. Semin Oncol [Suppl 2] 17: 30–34Google Scholar
  3. 3.
    Andreeff M, Gaynor J, Chapman D et al. (1987) Prognostic factors in acute lymphoblastic leukemia in adults: the Memorial Hospital experience in haematology and blood transfusion. In: Buechner T, Schellong G, Hiddemann W, Urbaniz D, Ritter W (eds) Acute leukemias. Springer, Berlin Heidelberg New York, pp 111–124CrossRefGoogle Scholar
  4. 4.
    Riehm H, Gadner H, Henze G et al. (1983) Acute lymphoblastic leukemia: treatment results in three BFM studies (1970-1981). In: Murphy S, Gilbert J (eds) Leukemia research: advances in cell biology and treatment. Elsevier, New York, pp 250–251Google Scholar
  5. 5.
    Hoelzer D, Thiel E, Loffler H et al. (1984) Intensified therapy in acute lymphoblastic and acute undifferentiated leukemia in adults. Blood 64: 38 - 47PubMedGoogle Scholar
  6. 6.
    Bostrom B, Brunning RD, McGlave P et al. (1985) Bone marrow transplantation for acute nonlymphocytic leukemia in first remission: analysis of prognostic factors. Blood 65: 1191–1196PubMedGoogle Scholar
  7. 7.
    Estey E, Smith TL, Keating MJ et al. (1989) Prediction of survival during induction therapy in patients with newly diagnosed acute myeloblasts leukemia. Leukemia 3: 257–263PubMedGoogle Scholar
  8. 8.
    Gaynor J, Chapman D, Little C et al. (1988) A cause-specific hazard rate analysis of prognostic factors among adult patients with acute lymphoblastic leukemia: the Memorial Hospital experience. J Clin Oncol 6: 1014–1030PubMedGoogle Scholar
  9. 9.
    Estey E, Plunkett W, Dixon D et al. (1987) Variables predicting response to high-dose cytosine arabinoside therapy in patients with refractory acute leukemia. Leukemia 1: 580–583PubMedGoogle Scholar
  10. 10.
    Andreeff M, Assing G, Cirrincione C (1986)Prognostic value of DNA/RNA flow cytome try in myeloblasts and lymphoblastic leukemia in adults: RNA content and S-phase predict remission duration and survival in multi-variate analysis. In: Andreeff M (ed) Clinical cytometry. Ann NY Acad Sci 468: 387–406Google Scholar
  11. 11.
    Andreeff M (1986) Cell kinetics of leukemia. Semin Hematol 23: 300–314PubMedGoogle Scholar
  12. 12.
    Andreeff M, Darynkiewicz Z, Sharpless TK et al. (1980) Discrimination of human leukemia subtypes by flow cytometric analysis of cellular DNA and RNA. Blood 55: 282–293PubMedGoogle Scholar
  13. 13.
    Redner A, Andreeff M, Bagin R et al. (1984) RNA content predicts early response in pediatric ALL: multivariate analysis of prognostic factors. Blood 64 [Suppl l]: 149aGoogle Scholar
  14. 14.
    Andreeff M, Espiritu E, Welte K (1986) Induction of interleukin-2 (IL-2) receptor and natural killer (NK) antigen expression by interleukin-2 and TPA treatment of acute lymphoid leukemic cells. Blood 68 [Suppl 1]: 216 aGoogle Scholar
  15. 15.
    Ellwart JW, Kremer JP, Doermer P (1988) Drug testing in established cell lines by flow cytometric vitality measurements versus clonogenic assay. Cancer Res 48: 5722–5725PubMedGoogle Scholar
  16. 16.
    Dolbeare F, Gratzner H, Pallavicini MG et al. (1983) Flow cytometric measurement of total DNA content and incorporated bromodeoxyuridine. Proc Natl Acad Sei USA 80: 5573–5577CrossRefGoogle Scholar
  17. 17.
    Gerdes J, Lemke H, Baisch HM (1984) Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki67. J Immunol 133: 1710–1715PubMedGoogle Scholar
  18. 18.
    Larsen JK, Christensen IJ, Mortensen BT etal. (1987) Growth fraction/DNA analyses using Ki67 antibody in flow cytometry of nuclear suspensions. Proceedings of the XVth meeting of the European Study Group for Cell ProliferationGoogle Scholar
  19. 19.
    Redner A, Groshen S, Melamed MR etal. (1983) Flow cytometry of ALL during induction therapy and multivariate analysis of prognostic factors. Proceedings of the symposium “Clinical Cytometry”, 1983, Sea Island, GA, p 109Google Scholar
  20. 20.
    Andreeff M, Kempin S, Arlin Z et al. (1983) High dose cytosine-arabinoside (HDARAC) in acute leukemia (AL): correlation of clinical response and cell kinetics. Proc Am Assoc Cancer Res 24: 166Google Scholar
  21. 21.
    Arlin ZA, Hagenbeek A, Feldman E etal. (1989) Implications of leukemia cell kill for the treatment of acute myelogenous leukemia (AML): can the cure rate be increased? Acta Haematol (in press)Google Scholar
  22. 22.
    Strife A, Lambek C, Wisniewski D et al. (1987) Activities of four purified growth factors on highly enriched human hematopoietic progenitor cells. Blood 69: 1508–1523PubMedGoogle Scholar
  23. 23.
    Deiwel R, Salem M, Pellens C etal. (1988) Growth regulation of human acute myeloid leukemia: effects of five recombinant hematopoietic factors in a serum-free system. Blood 72: 1944–1949Google Scholar
  24. 24.
    Asano Y, Shibuya T. Okamura S et al. (1987) Effect of human recombinant granulocyte/ macrophage colony-stimulating factor and nature granulocytic colony-stimulating factor on clonogenic leukemia blast cells. Cancer Res 47: 5647–5648PubMedGoogle Scholar
  25. 25.
    Loewenberg B, Salem M, Deiwel R (1988) Effect of recombinant multi-CSF, GM-CSF, G-CSF and M-CSF on the proliferation and maturation of human AML in vitro. Blood Cells 14: 539–549Google Scholar
  26. 26.
    Lista P, Brizzi MF, Avanzi G etal. (1988) Induction of proliferation of acute myeloblasts leukemia ( AML) cells with hemopoietic growth factors. Leuk Res 12: 441–447PubMedCrossRefGoogle Scholar
  27. 27.
    Murohashi K, Nagata K, Suzuki T et al. (1988) Effects of recombinant G-CSF and GM-CSF on the growth in methylocellulose and suspension of the blast cells in acute myeloblastic leukemia. Leuk Res 12: 433–440PubMedCrossRefGoogle Scholar
  28. 28.
    Vellenga E, Ostapovicz D, O’Rourke B et al. (1987) Effect of recombinant IL-3, GM-CSF and G-CSF on proliferation of leukemic clonogenic cells in short-term and long-term cultures. Leukemia 1: 584–589PubMedGoogle Scholar
  29. 29.
    Koike K, Ogawa M, Ihle JN et al. (1987) Recombinant murine granulocyte macrophage (GM) colony-stimulating factor support formation of GM and multipotent blast cell colonies in culture. Comparison with the effects of interleukin-3. J Cell Phys 131: 458CrossRefGoogle Scholar
  30. 30.
    Kaufman DC, Baer MR, Gao XZ etal. (1988) Enhanced expression of the granulocyte- macrophage colony stimulating factor gene in acute myelocytic leukemia cells following in vitro blast cell enrichment. Blood 72: 1329 - 1332PubMedGoogle Scholar
  31. 31.
    Sullivan DN, Glison BS, Hodges PK etal. (1986) Proliferation dependence of topoisomerase II mediated drug action. Biochemistry 25: 2248PubMedCrossRefGoogle Scholar
  32. 32.
    Tafuri A, Hegewisch S, Souza L et al. (1988) Stimulation of leukemic blast cells in vitro by colony stimulating factors (G-CSF, GMCSF) and interleukin-3 (IL-3): evidence of recruitment and increased cell killing with cytosine arabinoside (Ara-C). Blood 72 [Suppl 1]: 105 aGoogle Scholar
  33. 33.
    Andreeff M, Welte K (1989) Hematopoetic colony-stimulating factors. Semin Oncol 16: 211–219PubMedGoogle Scholar
  34. 34.
    Andreeff M, Hegewisch-Becker S, Tafuri A (1989) Recruitment of leukemic cells in vitro by colony-stimulating factors (G-CSF, GMCSF, Interleukin-3): evidence of increased cell kill and of differentiation by high- and lowdose cytosine-arabinoside. Blut (in press)Google Scholar
  35. 35.
    Cannistra SA, Groshek P, Griffin JD (1988) GM-CSF enhances the cytotoxic effects of cytosine arabinoside in acute myeloblasts leukemia and in the myeloid blast crisis phase of chronic myeloid leukemia. Blood 72 [Suppl 1]: 193 aGoogle Scholar
  36. 36.
    Lista P, Porcu P, Avanzi GC et al. (1988) Interleukin-3 enhances the cytotoxic activity of 1-B-D-arabinofurocytosine (Ara-C) on acute myeloblasts leukemia ( AML) cells. Br J of Haematol 69: 121–123CrossRefGoogle Scholar
  37. 37.
    Miyauchi J, Kelleher CA, Wang C et al. (1989) Growth factors influence the sensitivity of leukemic stem cells to cytosine arabinoside in culture. Blood 73: 1272–1278PubMedGoogle Scholar
  38. 38.
    A Sullivan DN, Glison BS, Hodges PK, Smallwood-Kentro S, Ross WE (1986) Proliferation dependence of topoisomerase II mediated drug action. Biochemistry 25: 2248PubMedCrossRefGoogle Scholar
  39. 39.
    Bhalla K, Birkhofer M, Arlin Z etal. (1988) Effect of recombinant GM-CSF on the metabolism of cytosine arabinoside in normal and leukemic bone marrow cells. Leukemia 2: 810–813PubMedGoogle Scholar
  40. 40.
    Gentile P, Broxmeyer HE (1983) Suppression of mouse myelopoiesis by administration of human lactoferrin in vivo and the comparative action of human transferrin. Blood 61: 982–993PubMedGoogle Scholar
  41. 41.
    Hittelman WN, Broussard LC, McCredie K (1979) Premature chromosome condensation studies in human leukemia. I. Pretreatment characteristics. Blood 54: 1001PubMedGoogle Scholar
  42. 42.
    Hittelmann W, Broussard K, Dosik G etal. (1980) Predicting relapse of human leukemia by means of premature chromosome condensation. N Engl J Med 303: 479–484CrossRefGoogle Scholar
  43. 43.
    Pinkel D, Straume T, Gray JW (1986) Cytogenetic analysis using quantitative, high-sensitivity, fluorescence hybridization. Proc Natl Acad Sci USA 83: 2934–2938PubMedCrossRefGoogle Scholar
  44. 44.
    Souza L, Boone T, Gabrilove etal. (1986) Recombinant human granulocyte colonystimulating factor: effects on normal and leukemic myeloid cells. Science 232:61–65PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • M. Andreeff
    • 1
    • 2
  • A. Tafuri
    • 1
  • S. Hegewisch-Becker
    • 1
  1. 1.Leukemia Cell Biology Laboratory, Memorial Sloan-Kettering Cancer CenterCornell University Medical College New YorkUSA
  2. 2.Hematology/Lymphoma Service, Department of Medicine, Memorial Sloan-Kettering Cancer CenterCornell University Medical College New YorkUSA

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