Advertisement

The Regulation of Blast Stem Cell Self-Renewal in Myeloblastic Leukemia

  • E. A. McCulloch
Conference paper
Part of the Experimental Hematology Today—1988 book series (HEMATOLOGY, volume 1988)

Abstract

The blast cells of Acute Myeloblastic Leukemia are considered as a novel lineage, composed of segments of normal differentiation programs assembled abnormally, reflecting abnormal gene expression. AML blast cells can be grown in culture; the earliest blast progenitors have been shown to have the stem cell capacity of self-renewal. This paper considers certain aspects of self-renewal regulation. First, based on drug survival curves measured in two culture techniques, the suggestion is made that the balance between self-renewal and differentiation is regulated by specific genes. Second evidence is presented that blast proliferative patterns are affected by the growth factors IL-3, GM-CSF, G-CSF and CSF-1. The most consistent pattern is seen with CSF-1, where cells show decreased self-renewal when exposed to CSF-1 added to cultures or to the products of the CSF-1 gene as detected by Northern analysis. Finally, the importance of self-renewal is emphasized. It is proposed that drugs might be classified by their effect on this crucial cell function; further, that the chemosensitivity of self-renewal is an attribute contributing to clinical outcome.

Keywords

Blast Cell Cytosine Arabinoside Acute Myeloblastic Leukemia Acute Myeloblastic Leukemia Patient Hemopoietic Growth Factor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    McCulloch EA, Till JE (1981) Blast cells in acute myeloblastic leukemia: A model. Blood Cells 7: 63–77.Google Scholar
  2. 2.
    Griffin JD, Lowenberg B (1986) Clonogenic cells in acute myeloblastic leukemia. Blood 68: 1185–1195.PubMedGoogle Scholar
  3. 3.
    Buick RN, Till JE, McCulloch EA (1977) Colony assay for proliferative blast cells circulating in myeloblastic leukaemia. Lancet 1: 862–863.PubMedCrossRefGoogle Scholar
  4. 4.
    Buick RN, Minden MD, McCulloch EA (1979) Self-renewal in culture of proliferative blast progenitor cells in acute myeloblastic leukemia. Blood 54: 95–104.PubMedGoogle Scholar
  5. 5.
    Nara N, McCulloch EA (1985) The proliferation in suspension of the progenitors of the blast cells in acute myeloblastic leukemia. Blood 65: 1484–1493.PubMedGoogle Scholar
  6. 6.
    Langley GR, Smith LJ, McCulloch EA (1986) Adherent cells in cultures of blast progenitors in acute myeloblastic leukemia. Leukemia Res 10: 953–959.CrossRefGoogle Scholar
  7. 7.
    McCulloch EA (1984) The blast cells of acute myeloblastic leukemia. In: Clinics in Hematology. McCulloch EA: ed. Saunders, London, pp 503–515.Google Scholar
  8. 8.
    Fialkow PJ (1982) Cell lineages in hematopoietic neoplasia studied with glucose-6-phosphate dehydrogenase cell markers. In: J Cell Physiol (supplement 1 ). J. Cell Physiol Alan Liss. New York.Google Scholar
  9. 9.
    McCulloch EA (1987) lineage infidelity or lineage promiscuity? Leukemia 1: 235.PubMedGoogle Scholar
  10. 10.
    Motoji T, Hoang T, Tritchler D, McCulloch EA (1985) The effect of 5- azacytidine and its analogues on blast cell renewal in acute myeloblastic leukemia. Blood 65: 894–901.PubMedGoogle Scholar
  11. 11.
    Wang C, McCulloch EA (1987) The sensitivity to 5-azacytidine of blast progenitors in acute myeloblastic leukemia. Blood 69: 553–559.PubMedGoogle Scholar
  12. 12.
    Nara N, Curtis JE, Senn JS, Tritchler DL, McCulloch EA (1986) The sensitivity to cytosine arabinoside of the blast progenitors of acute myeloblastic leukemia. Blood 67: 762–769.PubMedGoogle Scholar
  13. 13.
    Nara N, Yamashita Y, Murohashi I, Tanikawa S, Imai Y, Aoki N (1987) The effects on leukemic clonogenic cells in murine myeloid leukemia of 1-beta-D-arabinofuranosylcytosine and the anthracyclines adriamycin, daunomycin, aclacinomycin and 4′-epidoxorubicin. Cancer Research 47: 2376–2379.PubMedGoogle Scholar
  14. 14.
    Myers CE (1982) Anthracyclines. In: Pharmacological Principles of Cancer Treatment. Chabner B: ed. W.B. Saunders Co., Philadelphia, pp 416–434.Google Scholar
  15. 15.
    Chabner BA (1982) Cytosine Arabinoside. In: Pharmocological Principle of Cancer Treatment. Chabmner BA: ed. W.B. Saunders, Philadephia, pp 387–401.Google Scholar
  16. 16.
    Riggs AD, PA Jones (1983) 5-methylcytosine, gene regulation, and cancer. Adv Cancer Res 40: 1–25.PubMedCrossRefGoogle Scholar
  17. 17.
    Taylor SM, Jones PA (1979) Multiple new phenotypes induced in 10 1/2 and 3T3 cells treated with 5-azacytidine. Cell 7: 771–779.CrossRefGoogle Scholar
  18. 18.
    McCulloch EA, Buick RN, Curtis JE, Messner HA, Senn JS (1981) The heritable nature of clonal characteristics in acute myeloblastic leukemia. Blood 58: 105–109.PubMedGoogle Scholar
  19. 19.
    McCulloch EA, Curtis JE, Messner HA, Senn JS, Germanson TP (1982) The contribution of blast cell properties to outcome variation in acute myeloblastic leukemia ( AML ). Blood 59: 601–608.PubMedGoogle Scholar
  20. 20.
    Curtis JE, Messner HA, Hasselback R, Elhakim TM, McCulloch EA (1984) Contributions of host- and disease-related attributes to the outcome of patients with acute myelogeneous leukemia ( AML ). J Clin Oncol 2: 253–259.PubMedGoogle Scholar
  21. 21.
    Curtis JE, Messner HA, Minden MD, Minkin S, McCulloch EA (1987) High dose cytosine arabinoside in the treatment of acute myeloblastic leukemia: Contributions to outcome of clinical and laboratory attributes. J. Clin. Oncol. 5: 532–543.PubMedGoogle Scholar
  22. 22.
    Wang C, Curtis JE, Senn JS, Tritchler DL, McCulloch EA (1987) Response to 5-azacytidine of leukemic blast cells in suspension: a biological parameter associated with response to chemotherapy. Leukemia 1: 753–756.PubMedGoogle Scholar
  23. 23.
    Metcalf D (1984) The hemopoietic colony-stimulating factors. Elsvier. Amsterdam.Google Scholar
  24. 24.
    Clark SC, Kamen R (1987) The human hematopoietic colony-stimulating factors. Science 236: 1229–1237.PubMedCrossRefGoogle Scholar
  25. 25.
    Kelleher C, Miyauchi J, Wong G, Clark S, Minden MD, McCulloch EA (1987) Synergism between recombinant growth factors, GM-CSF and G-CSF, acting on the blast cells of acute myeloblastic leukemia. Blood 69: 1498–1503.PubMedGoogle Scholar
  26. 26.
    Griffin JD, Young D, Herrman F, Wiper D, Wagner K, Sabbath DK (1986) Effects of recombinant GM-CSF on the proliferation of clonogenic cells in acute myeloblastic leukemia. Blood 67: 1448–1453.PubMedGoogle Scholar
  27. 27.
    Delwel R, Dorssers L, Touw I, Wagemaker ER, Lowenberg B (1987) Human recombinant multilineage colony stimulating factor (Interleukin-3): stimulator of acute myelocytic leukemia progenitor cells in vitro. Blood 70: 333–336.PubMedGoogle Scholar
  28. 28.
    Nara N, Murohashi I, Suzuki T, Yamashita Y, Maruyama Y, Aoki N, Tanikawa S (1987) Effects of recombinant human granulocyte colony-stimulating factor ( G-CSF) on blast progenitors from acute myeloblastic leukaemia patients. Br J Cancer 56: 49–51.PubMedCrossRefGoogle Scholar
  29. 29.
    Miyauchi J, Wang C, Kelleher CA, Wong GG, Clark SC, Minden MD, McCulloch EA (1988) The effects of recombinant CSF-1 on the blast cells of acute myeloblastic leukemia in suspension culture. J Cell Physiol 135: 55–62.PubMedCrossRefGoogle Scholar
  30. 30.
    Sporn MB, Roberts AB (1985) Autocrine growth factors and cancer. Nature 313: 745–747.PubMedCrossRefGoogle Scholar
  31. 31.
    Cheng GYM, Kelleher CA, Miyauchi J, Wang C, Wong G, Clark S, McCulloch EA, Minden MD (1987) Structure and expression of genes of GM-CSF and G-CSF in blast cells from patients with Acute Myeloblastic Leukemia. Blood 71: 204–208.Google Scholar
  32. 32.
    Young DC, Wagner K, Griffin JD (1987) Constitutive expression of the granulocyte- macrophage colony-stimulating factor gene in acute meyloblastic leukemia. J Clin Invest 79: 100–106.PubMedCrossRefGoogle Scholar
  33. 33.
    Wang C, Kelleher CA, Cheng GYM, Miyauchi J, Wong GG, Clark SC, Minden MD, McCulloch EA (1988) Expression of the CSF-1 Gene in the Blast Cells of Acute Myeloblastic Leukemia: Association with Reduced Growth Capacity. J Cell Physiol 135: 133–138.PubMedCrossRefGoogle Scholar
  34. 34.
    Young DC, Demetri GD, Ernst TJ, Cannistra SA, Griffin JD (1988) In vitro expression of colony-stimulating factor genes in human acute myeloblastic leukemia cells. Exp Hematol 16: 378–382.PubMedGoogle Scholar
  35. 35.
    Sherr CJ, Rettenmier CW, Sacca R, Roussel MF, Look AT, Stanley ER (1985) The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1. Cell 41: 665–676.PubMedCrossRefGoogle Scholar
  36. 36.
    Till JE, McCulloch EA, Siminovitch L (1964) A stochastic model of stem cell proliferation, based on the growth of spleen colony forming cells. Proc Natl Acad Sci (USA) 51: 29–36.CrossRefGoogle Scholar
  37. 37.
    Nakahata T, Gross AJ, Ogawa M (1982) A stochastic model of self-renewal and committment to differentiation of the primitive hemopoietic stem cells in culture. J Cell Physiol 113: 455–458.PubMedCrossRefGoogle Scholar
  38. 38.
    Sachs L (1978) Control of normal cell differentiation in the phenotypic reversion of malignancy in myeloid leukemia. Nature 274: 535–539.PubMedCrossRefGoogle Scholar
  39. 39.
    Fung MC, Hapel AJ, Ymer S, Cohen DR, Johnson RM, Campbell HD, Young IG (1984) Molecular cloning of cDNA for murine interleukin-3. Nature 307: 233–237.PubMedCrossRefGoogle Scholar
  40. 40.
    Donahue RE, Seehra J, Norton C, Turner K, Metzger M, Rock, B, Carbone S, Seghal, R, Yang YC, Clark SC (1987) Stimulation of hematopoiesis in primates with human interleukin-3 and granulocyte-macrophage colony stimulating factor. Blood 70: 133a (abstr).Google Scholar
  41. 41.
    Messner HA, Yamasaki K, Jamal N, Minden MD, Wong GG, Clark SC (1987) Growth of human hemopoietic colonies in response to recombinant gibbon interleukin 3: Commparison with human recombinant granulocyte-macrophage colony-stimulating factor(GM-CSF). Proc Natl Acad Sci USA 84: 1–5.CrossRefGoogle Scholar
  42. 42.
    Yang Y-C, Ciarletta AB, Temple PA, Chung MP, Kovacic S, Witek-Gianotti JS, Leary AC, Kritz R, Donahue RE, Wong G-G, Clark SC (1986) Human IL- 3(Multi-CSF): Identification by expression cloning of a novel hemopoietic growth factor related to murine IL-3. Cell 47: 3–10.PubMedCrossRefGoogle Scholar
  43. 43.
    Mufson RA, Gesner TG, Turner K, Norton C, Yang Y-C, Clark S (1987) Characterization of IL-3 receptors on human acute myelogenous leukemia cell line KG-1. Blood 70: suppl 1, 118a.Google Scholar
  44. 44.
    Gough NM, Gough J, Metcalf D, Kelso A, Grail D, Nicola N, Burgess AW, Dunn AR (1984) Molecular cloning of cDNA encoding a murine hematopoietic growth regulator, granulocyte-macrophage colony stimulating factor. Nature 309: 763–767.PubMedCrossRefGoogle Scholar
  45. 45.
    Metcalf D (1986) The molecular biology and functions of the granulocyte-macrophage colony-stimulating factors. Blood 67: 257–267.PubMedGoogle Scholar
  46. 46.
    Miyatake S, Otsuka T, Yokota T, Lee F, Arai K (1985) Structure of the chromosomal gene for granulocyte-macrophage colony-stimulating factor: comparison of the mouse and human genes. Embo J 4: 2561–2568.PubMedGoogle Scholar
  47. 47.
    Sieff CA, Emerson SG, Donahue RE, Nathan DG, Wang EA, Wong GG, Clark SC (1985) Human recombinant granulocyte-macrophage colony-stimulating Factor: A Multilineage Hematoprotein. Science 230: 1171.PubMedCrossRefGoogle Scholar
  48. 48.
    Burgess AW, Begley, GC, Johnson GR, Lopez AF, Williamson DJ, Mermod JJ, Simpson RJ, Schmitz A, DeLmarter JF (1987) Purification and properties of bacterially synthesized human granulocyte-macrophage colony stimulating factor. Blood 69: 43–51.PubMedGoogle Scholar
  49. 49.
    Groopman JE, Mitysyasu RT, Deleo MJ, Oette DH, Golde DW (1987) Effect of recombinant human granulocyte-macrophage colony-stimulating factor on myelopoiesis in the acquired immunodeficiency syndrome. N Eng J Med 317: 593–598.CrossRefGoogle Scholar
  50. 50.
    Vadhan-Raj S, Keating M, LeMaistre, A, Hittleman WN, McCredie K, Trujillo JM, Broxmeyer HE, Henney C, Gutterman JU (1987) Effects of recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes. New Engl. J. Med. 25: 1545–1552.CrossRefGoogle Scholar
  51. 51.
    Souza LM, Boone, TC, Gabrilove J, Lai PH, Zsebo KM, Murdock DC, Chazin VR, Bruszewski J, Lu H, Chen KK, Barendt J, Platzer E, Moore MAS, Mertelsmann R, Welte, K (1986) Recombinant human granulocyte colony-stimulating factor: effects on normal and leukemic myeloid cells. Science 232: 61–65.PubMedCrossRefGoogle Scholar
  52. 52.
    Nagata S, Tsuchiya M, Asano S, Kaziro Y, Yamazaki T, Yamamoto O, Hirata Y, Kubota N, Oheda M, Nomura H, Ono M (1986) Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor. Nature 319: 415–417.PubMedCrossRefGoogle Scholar
  53. 53.
    Nagata S, Tsuchiya T, Asano S, Yamamoto O, Hirata Y, Kubota N, Yasmazaki T (1986) The chromosome gene structure and two mRNAs for human granulocyte colony-stimulating factor. Embo J 5: 575–581.PubMedGoogle Scholar
  54. 54.
    Nomura H, Imazeki I, Oheda M, Kubota N, Tamura M, Ono M, Ueyama Y, Asano S (1986) Purification and characterization of human granulocyte colony stimulating factor ( G-CSF ). EMBO J 5: 871.PubMedGoogle Scholar
  55. 55.
    Shimamura M, Kobayashi Y, Yuo A, Urabe A, Okabe T, Komatsu Y, Itoh S, Takaku F (1987) Effect of human recombinant granulocyte colony-stimulating factor on hemopoietic injury in mice induced by 5-fluorouracil. Blood 69: 353–355.PubMedGoogle Scholar
  56. 56.
    Welte K, Bonilla MA, Gillo AP, Boone TC, Potter GK, Gabrilove JL, Moore MAS, O’Reilly RJ, Souza LM (1987) Recombinant human granulocyte colony-stimulating factor: effects on hematopoiesis in normal and cyclophosphamide-treated primates. J Exp Med 165: 941–948.PubMedCrossRefGoogle Scholar
  57. 57.
    Yuo A, Kitagawa S, Okabe T, Urabe A, Komatsu Y, Itoh S, Takaku F (1987) Recombinant human granulocyte colony-stimulating factor repairs the abnormalities of neutrophils in patients with myelodysplastic syndromes and chronic myelogenous leukemia. Blood 70: 404–411.PubMedGoogle Scholar
  58. 58.
    Stanley ER, Guilbert LJ, Tushinski RJ, Bartelmez SH (1983) CSF-1: a mononuclear phagocyte lineage-specific hemopoietic growth factor. J Cell Biochem 21: 151–159.PubMedCrossRefGoogle Scholar
  59. 59.
    Das SK, Stanley ER (1982) Structure-funtion studies of a colony stimulating factor (CSF-1). J Biol Chem 257: 13679–13684.PubMedGoogle Scholar
  60. 60.
    Wong GG, Temple PA, Leary A, Witek-Giannotti JS, Yang Y, Ciarletta AB, Chung M, Murtha P, Kritz R, Kaufman RJ, Ferenz CR, Sibley BS, Turner KJ, Hewick RM, Clark SC, Yanai N, Yokota H, Yamada M (1987) Human CSF-1: Molecular cloning and expression of 4-kb cDNA encoding the human urinary protein. Science 235: 1504–1508.PubMedCrossRefGoogle Scholar
  61. 61.
    Rambaldi A, Young DC, Griffin JD (1987) Expression of the M-CSF (CSF-1) gene by human monocytes. Blood 69: 1409–1413.PubMedGoogle Scholar
  62. 62.
    Goldwasser E (1976) Erythropoietin and the differentiation of red blood cells. Fed Proc 34: 2285–2292.Google Scholar
  63. 63.
    Jacobs K, Shoemaker C, Rudersdorph R, Neil SD, Kaufman RJ, Mufson A, Seehra J, Jones SS, Hewick R, Fritsh EF, Kawakita M, Shimizu T, Miyake T (1985) Isolation and characterization of genomic and cDNA clones of human erythropoietin. Nature 313: 806–810.PubMedCrossRefGoogle Scholar
  64. 64.
    Eschbach JW, Egrie JC, Downing MR, Browne JK, Adamson JW (1987) Correcton of the anemia of end-stage renal disease with recombinant human erythropoietin. N Engl J Med 316: 73–78.PubMedCrossRefGoogle Scholar
  65. 65.
    Lin FK, Suggu S, Lin CH, Browne JK, Smalling R, Egrie JC, Chen KK, Fox GM, Martin F, Stabinsky Z, Badrawi SM, Lai PH, Goldwasser E (1985) Cloning and expression of the human erythropoietin gene. Proc Natl Acad Sci (USA) 82: 7580.CrossRefGoogle Scholar
  66. 66.
    Mochizuki DY, Eisenman JR, Conlon PJ, Larsen AD, Tushinski RJ (1987) Interleukin-1 regulates hematopoietic activity, a role previously ascribed to hemopoietin-1. Proc Natl Acad Sci. 84: 5267–5271.PubMedCrossRefGoogle Scholar
  67. 67.
    Bird TA, Skalatvala J (1986) Identification of a common class of high affinity receptors for both types of interleukin-1 on connective tissue cells. Nature 324: 263–266.PubMedCrossRefGoogle Scholar
  68. 68.
    Dower SK, Kronheim SR, Hopp TP, Cantrell M, Deely M, Gillis S, Henney CS, Urdal Dl (1986) The cell surface receptors for Interleukin-1 alpha and interleukin-1 beta are identical. Nature 324: 266–268.PubMedCrossRefGoogle Scholar
  69. 69.
    Zucali JR, Dinarello CA, Oblon DJ, Gross MA, Anderson L, Weiner RS (1986) Interleukin 1 stimulates fibroblasts to produce granulocyte-macrophage colony stimulating activity (GM-CSA) and prostoglandin E2 (PGE2). J Clin Invest 77: 1837.CrossRefGoogle Scholar
  70. 70.
    Broudy VC, Kaushansky K, Harlan JM, Adamson JW (1987) Interleukin-1 stimulates human endothelial cells to produce granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor. J Immunol 139: 464–468.PubMedGoogle Scholar
  71. 71.
    Lee F, Yokota, T, Otsuka T, Meyerson P, Villaret D, Coffman R, Mosman T, Rennick D, Roehm N, Smith C, Zlotnick A, Arai K-I (1986) Isolation and characterization of a mouse interleukin cDNA clone that expresses BSF-1 activities and T cell and mast cell sttimulating activities. Proc Natl Acad Sci (USA) 83: 2061–2065.CrossRefGoogle Scholar
  72. 72.
    O’Garra A, Warren DJ, Holman M, Popham AM, Sanderson CJ, Klaus GBB (1986) Interleukin 4 ( B-cell growth factorII/eosinophil differentiation factor) is a mitogen and differentiation factor for preactivated murine B lymphocytes. Proc Natl Acad Sci (USA) 83: 5228–5232.CrossRefGoogle Scholar
  73. 73.
    Rennick D, Yang G, Muller-Sieburg C, Smith C, Arai N, Takabe Y, Gemmell L (1987) Interleukin 4 (B-cell stimulatory factor 1) can enhance or anatagonize the factor dependent growth of hemopoietic progenitor cells. Proc Natl Acad Sci USA 84: 6889–6893.PubMedCrossRefGoogle Scholar
  74. 74.
    Campbell HD, Tucker WQJ, Hort Y, Martinson ME, Mayo Gr Clutterbuck EJ, Sanderson CJ, Young IG (1987) Molecular cloning, nucleotide sequence, and expression of the gene encoding human eosinophil differentiation factor (interleukin 5). Proc Natl Acad Sci USA 84: 6629–6633.PubMedCrossRefGoogle Scholar
  75. 75.
    Ikebuchi K, Wong GG, Clark SC, Ihle JN, Hirai Y, Ogawa M (1987) Interleukin 6 enhancement of interleukin 3-dependent proliferation of multipotential hemopoietic progenitors. Proc Natl Acad Sci USA 84: 9035–9039.PubMedCrossRefGoogle Scholar
  76. 76.
    Garman RD, Jacobs KA, Clark SC, Raulet DH (1987) B-cell-stimulatory factor 2 (beta 2 interferon) functions as a second signal for interleukin 2 production by mature murine T cells. Proc Natl Acad Sci USA 84: 7629–7633.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • E. A. McCulloch

There are no affiliations available

Personalised recommendations