Cellular and Molecular Aspects of Myeloid Cell Proliferation and Development

  • Caroline A. Evans
  • Andrew Pierce
Part of the Blood Cell Biochemistry book series (BLBI, volume 7)


Stem cells give rise to all the different types of blood cell. These pluripotent cells undergo self-renewal and differentiation to produce more developmentally restricted cells, which proliferate and develop to form mature cells. Hematopoietic stem cells are defined by their ability to establish long-term reconstitution of hematopoiesis when transplanted to irradiated recipient animals (Till and McCulloch, 1961). Committed progenitor cells have a restricted developmental capacity; e.g., granulocyte—macrophage colony-forming cells (GM-CFC) or erythroid burst-forming units (BFU-e) can form only neutrophil, macrophage, or erythroid cells, respectively. Hematopoiesis occurs in the microenvironment of adult bone marrow where proliferation and differentiation of hematopoietic stem and progenitor cells occurs in close contact with the bone marrow stromal cells and the associated extracellular matrix (ECM) (Adams and Watt, 1993; Yoder and Williams, 1995). These interactions have been termed the local area network (LAN).


Progenitor Cell Acute Myeloid Leukemia Chronic Myeloid Leukemia Hematopoietic Cell Stem Cell 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.


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  1. Adams, J., and Watt, F., 1993, Regulation of development and differentiation by ECM, Development 117: 1183 1187.Google Scholar
  2. Adams, J. M., Houston, H., Allen, J., Lints, T., and Harvey, R., 1992, The hematopoietically expressed vav proto-oncogene shares homology with the dbl GDP—GTP exchange factor, the bcr gene and a yeast gene (CDC24) involved in cytoskeletal organization, Oncogene 7(4): 611–618.PubMedGoogle Scholar
  3. Baines, P., and Visser, J. W., 1983, Analysis and separation of murine bone marrow stem cells by H33342 fluorescence-activated cell sorting, Exp. Hematol. 11(8): 701–708.PubMedGoogle Scholar
  4. Bashey, A., Gill, R., Levi, S., Farr, C. J., Clutterbuck, R., Millar, J. L., Pragnell, I. B., and Marshall, C. J., 1992, Mutational activation of the N-ras oncogene assessed in primary clonogenic culture of acute myeloid leukemia (AML): Implications for the role of N-ras mutation in AML pathogenesis, Blood 79(4): 981–989.PubMedGoogle Scholar
  5. Baum, C. M., Weissman, I. L., Tsukamoto, A. S., Buckle, A. M., and Peault, B., 1992, Isolation of a candidate human hematopoietic stem-cell population, Proc. Natl. Acad. Sci. U.S.A. 89(7): 2804–2808.PubMedCrossRefGoogle Scholar
  6. Benit, L., Courtois, G., Charon, M., Varlet, P., Dusanter, F. I., and Gisselbrecht, S., 1994, Characterization of mpl cytoplasmic domain sequences required for myeloproliferative leukemia virus pathogenicity, J. Virol. 68(8): 5270–5274.PubMedGoogle Scholar
  7. Bertoncello, I., Bradley, T. R., Hodgson, G. S., and Dunlop, J. M., 1991, The resolution, enrichment, and organization of normal bone marrow high proliferative potential colony-forming cell subsets on the basis of rhodamine-123 fluorescence, Exp. Hematol. 19(3): 174–178.PubMedGoogle Scholar
  8. Bi, S., Barton, C. M., Lemoine, N. R., Cross, N. C., and Goldman, J. M., 1994, Retroviral transduction of Philadelphia-positive chronic myeloid leukemia cells with a human mutant p53 cDNA and its effect on in vitro proliferation [see comments], Exp. Hematol. 22(1): 95–99.PubMedGoogle Scholar
  9. Brandt, J., Baird, N. Lu, L., Srour, E., and Hoffman, R., 1988, Characterization of a human hematopoietic progenitor cell capable of forming blast cell containing colonies in vitro, J. Clin. Invest. 82(3): 1017–1027.Google Scholar
  10. Brannan, C. I., Lyman, S. D. Williams, D. E., Eisenman, J., Anderson, D. M., Cosman, D., Bedell, M. A., Jenkins N. A., and Copeland, N.G., 1991, Steel–Dickie mutation encodes a c-kit ligand lacking transmembrane and cytoplasmic domains, Proc. Natl. Acad. Sci. U.S.A. 88(11): 4671–4674.CrossRefGoogle Scholar
  11. Broudy, V. C., Lin, N. L., and Kaushansky, K., 1995, Thrombopoietin (c-mpl ligand) acts synergistically with erythropoietin, stem cell factor, and interleukin-11 to enhance murine megakaryocyte colony growth and increases megakaryocyte ploidy in vitro, Blood 85(7): 1719–1726.PubMedGoogle Scholar
  12. Broxmeyer, H. E., Sherry, B., Cooper, S., Lu, L., Maze, R., Beckmann, M. P., Cerami, A., and Ralph, P., 1993, Comparative analysis of the human macrophage inflammatory protein family of cytokines (chemokines) on proliferation of human myeloid progenitor cells. Interacting effects involving suppression, synergistic suppression, and blocking of suppression, J. Immunol. 150: 3448–3458.PubMedGoogle Scholar
  13. Carlesso, N., Griffin, J.D., and Druker, J., 1994, Use of a temperature-sensitive mutant to define the biological effects of the p210BCR-ABL tyrosine kinase on proliferation of a factor-dependent murine myeloid cell line, Oncogene 9 (1): 149–156.PubMedGoogle Scholar
  14. Caux, C., Saeland, S., Favre, C., Duvert, V., Mannoni, P., and Banchereau, J., 1990, Tumor necrosis factor-alpha strongly potentiates interleukin-3 and granulocyte–macrophage colony-stimulating factor-induced proliferation of human CD34+ hematopoietic progenitor cells, Blood 75 (12): 2292–2298.PubMedGoogle Scholar
  15. Champlin, R. E., and Golde, D. W., 1985, Chronic myelogenous leukaemia: Recent advances, Blood 65: 1039 1047.Google Scholar
  16. Chung, S. W., Wong, P. M., Durkin, H., Wu, Y. S., and Petersen, J., 1991, Leukemia initiated by hemopoietic stem cells expressing the v-abl oncogene, Proc. Natl. Acad. Sci. U.S.A. 88 (4): 1585–1589.PubMedCrossRefGoogle Scholar
  17. Civin, C. I., Strauss, L. C., Fackler, M. J., Trischmann, T. M., Wiley, J. M., and Loken, M.R., 1990, Positive stem cell selection—basic science, Prog. Clin. Biol. Res. 333 (387): 387–401.PubMedGoogle Scholar
  18. Courtneidge, S. A., Dhand, R., Pilat, D., Twamley, G. M., Waterfield, M. D., and Roussel, M.F., 1993, Activation of Src family kinases by colony stimulating factor-1, and their association with its receptor, EMBO J. 12 (3): 943–950.PubMedGoogle Scholar
  19. Courtois, G., Benit, L., Mikaeloff, Y., Pauchard, M., Charon, M., Varlet, P., and Gisselbrecht, S., 1995, Constitutive activation of a variant of the env-mpl oncogene product by disulfide-linked homodimerization, J. Virol. 69 (5): 2794–2800.PubMedGoogle Scholar
  20. Daley, G. Q., and Baltimore, D., 1988, Transformation of an interleukin 3-dependent hematopoietic cell line by the chronic myelogenous leukemia-specific P210bcr/abl protein, Proc. Natl. Acad. Sci. U.S.A. 85 (23): 9312–9316.PubMedCrossRefGoogle Scholar
  21. Daley, G. Q., Van Etten, R.A., and Baltimore, D., 1990, Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome, Science 247: 824–830.PubMedCrossRefGoogle Scholar
  22. D’Andrea, A. D., Fasman, G. D., and Lodish, H.F., 1989, Erythropoietin receptor and interleukin-2 receptor beta chain: a new receptor family, Cell 58 (6): 1023–1024.PubMedCrossRefGoogle Scholar
  23. D’Andrea, A. D., Yoshimura, A., Youssoufian, H., Zon, L. I., Koo, J. W., and Lodish, H.F., 1991, The cytoplasmic region of the erythropoietin receptor contains nonoverlapping positive and negative growth-regulatory domains, Mol. Cell Biol. U(4): 1980–1987.Google Scholar
  24. Debili, N., Wendling, F., Cosman, D., Titeux, M., Florindo, C., Dusanter, F. I., Schooley, K., Methia, N., Charon, M., Nador, R., Bettaieb, A., and Vainchenker, W., 1995, The Mpl receptor is expressed in the megakaryocytic lineage from late progenitors to platelets, Blood 85 (2): 391–401.Google Scholar
  25. de la Chapelle, A., Sistonen, P., Lehvaslaiho, H., Ikkala, E., and Juvonen, E., 1993a, Familial erythrocytosis genetically linked to erythropoietin receptor gene, Lancet 341: 82–84.PubMedCrossRefGoogle Scholar
  26. de la Chapelle, A., Traskelin, A. L., and Juvonen, E., 1993b, Truncated erythropoietin receptor causes dominantly inherited benign human erythrocytosis, Proc. Natl. Acad. Sci. U.S.A. 90(10): 4495–4499.PubMedCrossRefGoogle Scholar
  27. Dhut, S., Chaplin, T., and Young, B. D., 1991, Normal c-abl gene protein—a nuclear component, Oncogene 6: 1459–1464.PubMedGoogle Scholar
  28. Diekmann, D., Brill, S., Garrett, M. D., Totty, N., Hsuan, J., Monfries, C., Hall, C., Lim, L., and Hall, A., 1991, Bcr encodes a GTPase-activating protein for p21 Rac, Nature 351: 400–402.Google Scholar
  29. Dosil, M., Wang, S., and Lemischka, I. R., 1993, Mitogenic signalling and substrate specificity of the Flk2/FIt3 receptor tyrosine kinase in fibroblasts and interleukin 3-dependent hematopoietic cells, Mol. Cell Biol. 13 (10): 6572–6585.PubMedGoogle Scholar
  30. Drachman, J. G., Griffin, J. D., and Kaushansky, K., 1995, The c-Mpl ligand (thrombopoietin) stimulates tyrosine phosphorylation of Jak2, Shc, and c-Mpl, J. Biol. Chem. 270(10): 4979–4982.PubMedCrossRefGoogle Scholar
  31. Eaves, C. J., Cashman, J. D., Kay, R. J., Dougherty, G. J., Otsuka, T., Gaboury, L. A., Hogge, D. E., Lansdorp, P. M., Eaves, A. C., and Humphries, R. K., 1991, Mechanisms that regulate the cell cycle status of very primitive hematopoietic cells in long-term human marrow cultures. Il. Analysis of positive and negative regulators produced by stromal cells within the adherent layer, Blood 78 (1): 110–117.PubMedGoogle Scholar
  32. Eaves, C. J., Cashman, J. D., Wolpe, S. D., and Eaves, A.C., 1993, Unresponsiveness of primitive chronic myeloid leukemia cells to macrophage inflammatory protein 1 alpha, an inhibitor of primitive normal hematopoietic cells, Proc. Natl. Acad. Sci. U.S.A. 90 (24): 12015–12019.PubMedCrossRefGoogle Scholar
  33. Elefanty, A. G., Hariharan, I. K., and Cory, S., 1990, bcr-abl,the hallmark of chronic myeloid leukemia in man, induces multiple neoplasms in mice, EMBO J. 9(4):1069–1078.Google Scholar
  34. Fichelson, S., Vigon, I., Dusanter, I., Charon, M., Velu, T., Baillou, C., Gisselbrecht, S., and Lemoine, F. M., 1995, In vitro transformation of murine pro-B and pre-B cells by v-mpl, a truncated form of a cytokine receptor, J. Immunol. 154 (4): 1577–1586.Google Scholar
  35. Flanagan, J. G., Chan, D. C., and Leder, P., 1991, Transmembrane form of the kit ligand growth factor is determined by alternative splicing and is missing in the Sld mutant, Cell 64 (5): 1025–1035.PubMedCrossRefGoogle Scholar
  36. Gishizky, M. L., and Witte, O.N., 1992, Initiation of deregulated growth of multipotent progenitor cells by bcr-abl in vitro, Science 256: 836–839.PubMedCrossRefGoogle Scholar
  37. Golub, T. R., Barker, G. F., Lovett, M., and Gilliland, D., 1994, Fusion of PDGF receptor beta to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation, Cell 77 (2): 307–316.PubMedCrossRefGoogle Scholar
  38. Gordon, M. Y., Riley, G. P., Watt, S. M., and Greaves, M. F., 1987, Compartmentalization of a hematopoietic growth factor (GM-CSF) by glycosaminoglycans in the bone marrow microenvironment, Nature 326: 403–405.PubMedCrossRefGoogle Scholar
  39. Gordon, M. Y., Atkinson, J., Clarke, D., Dowding, C. R., Goldman, J. M., Grimsley, P. G., Siczkowski, M., and Greaves, M. F., 1991, Deficiency of a phosphatidylinositol-anchored cell adhesion molecule influences hematopoietic progenitor binding to marrow stroma in chronic myeloid leukaemia, Leukemia 5 (8): 693–698.PubMedGoogle Scholar
  40. Gualtieri, R. J., Shadduck, R. K., Baker, D. G., and Quesenberry, P. J., 1984, Hematopoietic regulatory factors produced in long-term murine bone marrow cultures and the effect of in vitro irradiation, Blood 64 (2): 516–525.PubMedGoogle Scholar
  41. Gurney, A. L., Kuang, W. J., Xie, M. H., Malloy, B. E., Eaton, D. L., and de Sauvage, S. F., 1995, Genomic structure, chromosomal localization, and conserved alternative splice forms of thrombopoietin, Blood 85 (4): 981–988.PubMedGoogle Scholar
  42. Hannum, C., Culpepper, J., Campbell, D., McClanahan, T., Zurawski, S., Bazan, J. F., Kastelein, R., Hudak, S., Wagner, J., and Mattson, J., Luh, J., Duda, G., Martina, N., Peterson, D., Menon, S., Shanafelt, A., Muench, M., Keiner, G,. Namikawa, R., Rennick, D., Roncouolo, M.-G., Zlotnick, A., Rosnet, O, Dubreid, P., Birnbaum, D., and Lee, F., 1994, Ligand for FLT3/FLK2 receptor tyrosine kinase regulates growth of hematopoietic stem cells and is encoded by variant RNAs, Nature 368: 643–648.PubMedCrossRefGoogle Scholar
  43. Hariharan, I. K., Harris, A. W., Crawford, M., Abud, H., Webb, E., Cory, S., and Adams, J. M., 1989, A bcr-v-abl oncogene induces lymphomas in transgenic mice, Mol. Cell Biol. 9 (7): 2798–2805.PubMedGoogle Scholar
  44. Heisterkamp, N., Jenster, G., ten Hoeve, J., Zovich, D., Pattengale, P. K., and Groffen, J., 1990, Acute leukaemia in bcr/abl transgenic mice, Nature 344: 251–253.PubMedCrossRefGoogle Scholar
  45. Honda, H., Fujii, T., Takatoku, M., Mano, H., Witte, O. N., Yazaki, Y., and Hirai, H., 1995, Expression of p210bcr/abl by metallothionein promoter induced T-cell leukemia in transgenic mice, Blood 85(10): 2853–2861.PubMedGoogle Scholar
  46. Hunter, T., and Cooper, J. A., 1985, Protein-tyrosine kinases, Annu. Rev. Biochem. 54: 897–930.PubMedCrossRefGoogle Scholar
  47. Hynes, R., 1992, Integrins: Versatility, modulation and signalling in cell adhesion, Cell 69: 11–17.PubMedCrossRefGoogle Scholar
  48. Ichihara, M., Hara, T., Takagi, M., Cho, L. C., Gorman, D. M., and Miyajima, A., 1995, Impaired interleukin-3 (IL-3) response of the AJJ mouse is caused by a branch point deletion in the IL-3 receptor alpha subunit gene, EMBO J. 14 (5): 939–950.PubMedGoogle Scholar
  49. Ihle, J. N., Witthuhn, B., Tang, B., Yi, T., and Quelle, F. W., 1994, Cytokine receptors and signal transduction, Baillieres Clin. Haematol. 7 (1): 17–48.PubMedCrossRefGoogle Scholar
  50. Jacobsen, F. W., Rusten, L. S., and Jacobsen, S. E., 1994, Direct synergistic effects of interleukin-7 on in vitro myelopoiesis of human CD34+ bone marrow progenitors, Blood 84 (3): 775–779.PubMedGoogle Scholar
  51. Jacobsen, S. E., Ruscetti, F. W., Dubois, C. M., Wine, J., and Keller, J. R., 1992, Induction of colony-stimulating factor receptor expression on hematopoietic progenitor cells: Proposed mechanism for growth factor synergism, Blood 80 (3): 678–687.PubMedGoogle Scholar
  52. Jacobsen, S. E., Okkenhaug, C., Myklebust, J., Veiby, O.P., and Lyman, S.D., 1995, The FLT3 ligand potently and directly stimulates the growth and expansion of primitive murine bone marrow progenitor cells in vitro: Synergistic interactions with interleukin (IL)-11, IL-12, and other hematopoietic growth factors, J. Exp. Med. 181 (4): 1357–1363.PubMedCrossRefGoogle Scholar
  53. Jordan, C. T., McKearn, J. P., and Lemischka, I. R., 1990, Cellular and developmental properties of fetal hematopoietic stem cells, Cell 61 (6): 953–963.PubMedCrossRefGoogle Scholar
  54. Kaushansky, K., 1994, The mpl ligand: Molecular and cellular biology of the critical regulator of megakaryocyte development, Stem Cells Dayt. 1 (91): 91–96.Google Scholar
  55. Kaushansky, K., Broudy, V. C., Lin, N., Jorgensen, M. J., McCarty, J., Fox, N., Zucker, F. D., and Lofton, D. C., 1995, Thrombopoietin, the Mpl ligand, is essential for full megakaryocyte development, Proc. Natl. Acad. Sci. U.S.A. 92(8): 3234–3238.PubMedCrossRefGoogle Scholar
  56. Kelliher, M. A., McLaughlin, J., Witte, O. N., and Rosenberg, N., 1990, Induction of a chronic myelogenous leukemia-like syndrome in mice with v-abl and BCR/ABL [published erratum appears in Proc. Natl. Acad. Sci. U.S.A. 1990, 87(22):9072], Proc. Natl. Acad. Sci. U.S.A. 87 (17): 6649–6653.PubMedCrossRefGoogle Scholar
  57. Kipreos, E. T., and Wang, J. Y., 1992, Cell cycle-regulated binding of c-Abl tyrosine kinase to DNA, Science 256: 382–385.PubMedCrossRefGoogle Scholar
  58. Koury, M. J., 1992, Programmed cell death (apoptosis) in hematopoiesis, Exp. Hematol. 20 (4): 391–394.PubMedGoogle Scholar
  59. Krause, D. S., Ito, T., Fackler, M. J., Smith, O. M., Collector, M. I., Sharkis, S. J., and May, W. S., 1994, Characterization of murine CD34, a marker for hematopoietic progenitor and stem cells, Blood 84 (3): 691–701.PubMedGoogle Scholar
  60. Kubo, K., Naoe, T., Kiyoi, H., Fukutani, H., Kato, Y., Oguri, T., Yamamori, S., Akatsuka, Y. A., Kodera, Y., and Ohno, R., 1993, Clonal analysis of multiple point mutations in the N-ras gene in patients with acute myeloid leukemia, Jpn. J. Cancer Res. 84 (4): 379–387.PubMedCrossRefGoogle Scholar
  61. Laneuville, P., Sun, G., Timm, M., and Vekemans, M., 1992, Clonal evolution in a myeloid cell line transformed to interleukin-3 independent growth by retroviral transduction and expression of p210bcr/abl, Blood 80 (7): 1788–1797.PubMedGoogle Scholar
  62. Lev, S., Yarden, Y., and Givol, D., 1992a, Dimerization and activation of the kit receptor by monovalent and bivalent binding of the stem cell factor, J. Biol. Chem. 267 (22): 15970–15977.PubMedGoogle Scholar
  63. Lev, S., Yarden, Y., and Givol, D., 1992b, A recombinant ectodomain of the receptor for the stem cell factor (SCF) retains ligand-induced receptor dimerization and antagonizes SCF-stimulated cellular responses, J. Biol. Chem. 267 (15): 10866–10873.PubMedGoogle Scholar
  64. Lev, S., Givol, D., and Yarden, Y., 1992c, Interkinase domain of kit contains the binding site for phosphatidylinositol 3’ kinase, Proc. Natl. Acad. Sci. U.S.A. 89 (2): 678–682.PubMedCrossRefGoogle Scholar
  65. Liboi, E., Carroll, M., D’ Andrea, D.A., and Mathey, P. B., 1993, Erythropoietin receptor signals both proliferation and erythroid-specific differentiation, Proc. Natl. Acad. Sci. U.S.A. 90 (23): 11351–11355.PubMedCrossRefGoogle Scholar
  66. Lieschke, G. J., Grail, D., Hodgson, G., Metcalf, D., Stanley, E., Cheers, C., Fowler, K. J., Basu, S., Zhan, Y. F., and Dunn, A. R., 1994a, Mice lacking granulocyte colony-stimulating factor have chronic neutropenia, granulocyte and macrophage progenitor cell deficiency, and impaired neutrophil mobilization, Blood 84(6):17371746.Google Scholar
  67. Lieschke, G. J., Stanley, E., Grail, E., Hodgson, G., Sinickas, V., Gall, J. A., Sinclair, R. A., and Dunn, A. R., 1994b, Mice lacking both macrophage-and granulocyte—macrophage colony-stimulating factor have macrophages and coexistent osteopetrosis and severe lung disease, Blood 84 (1): 27–35.PubMedGoogle Scholar
  68. Lioubin, M. N., Myles, G. M., Carlberg, K., Bowtell, D., and Rohrschneider, L. R., 1994, Shc, Grb2, Sos I, and a 150-kilodalton tyrosine-phosphorylated protein form complexes with Fms in hematopoietic cells, Mol. Cell Biol. 14 (9): 5682–5691.PubMedCrossRefGoogle Scholar
  69. Lubbert, M., Oster, W., Knopf, H. P., McCormick, F., Mertelsmann, R., and Herrmann, F., 1993, N-RAS gene activation in acute myeloid leukemia: Association with expression of interleukin-6, Leukemia 7 (12): 1948–1954.Google Scholar
  70. Lugo, T. G., Pendergast, A. M., Muller, A. J., and Witte, O. N., 1990, Tyrosine kinase activity and transformation potency of bcr-abl oncogene products, Science 247: 1079–1082.PubMedCrossRefGoogle Scholar
  71. Lyman, S. D., Brasel, K., Rousseau, A. M., and Williams, D. E., 1994, The flt3 ligand: A hematopoietic stem cell factor whose activities are distinct from steel factor, Stem Cells Dayt. 1 (99): 99–107.Google Scholar
  72. Manu, Y., and Witte, O. N., 1991, The BCR gene encodes a novel serine/threonine kinase activity within a single exon, Cell 67 (3): 459–468.CrossRefGoogle Scholar
  73. Manu, Y., Peters, K. L., Afar, D. E., Shibuya, M., Witte, O. N. and Smithgall, T. E., 1995, Tyrosine phosphorylation of BCR by FPS/FES protein-tyrosine kinases induces association of BCR with GRB-2/SOS, Mol. Cell Biol. 15 (2): 835–842.Google Scholar
  74. Maruyama, K., Miyata, K., and Yoshimura, A., 1994, Proliferation and erythroid differentiation through the cytoplasmic domain of the erythropoietin receptor, J. Biol. Chem. 269(8): 5976–5980.PubMedGoogle Scholar
  75. Matthews, W., Jordan, C. T., Wiegand, G. W., Pardoll, D., and Lemischka, I. R., 1991a, A receptor tyrosine kinase specific to hematopoietic stem and progenitor cell-enriched populations, Cell 65(7): 1143–1152.PubMedCrossRefGoogle Scholar
  76. Matthews, W., Jordan, C. T., Gavin, M., Jenkins, N. A., Copeland, N. G., and Lemischka, I. R., 1991b, A receptor tyrosine kinase cDNA isolated from a population of enriched primitive hematopoietic cells and exhibiting close genetic linkage to c-kit, Proc. Natl. Acad. Sci. U.S.A. 88(20): 9026–9030.PubMedCrossRefGoogle Scholar
  77. McLaughlin, J., Chianese, E., and Witte, O. N., 1987, In vitro transformation of immature hematopoietic cells by the P210 BCR/ABL oncogene product of the Philadelphia chromosome, Proc. Natl. Acad. Sci. U.S.A. 84(18): 6558–6562.Google Scholar
  78. McLaughlin, J., Chianese, E., and Witte, O. N., 1989, Alternative forms of the BCR-ABL oncogene have quantitatively different potencies for stimulation of immature lymphoid cells, Mol. Cell Biol. 9(5): 1866–1874.PubMedGoogle Scholar
  79. McWhirter, J. R., and Wang, J. Y. J., 1991, Activation of tyrosine kinase and microfilament binding functions of c-abl by bcr sequences in bcr/abl fusion proteins, Mol. Cell Biol. 11: 1553–1565.PubMedGoogle Scholar
  80. McWhirter, J. R., Galasso, D. L., and Wang, J. Y., 1993, A coiled-coil oligomerization domain of Bcr is essential for the transforming function of Bcr-Abl oncoproteins, Mol. Cell Biol. 13(12): 7587–7595.PubMedGoogle Scholar
  81. Metcalf, D., 1995, The granulocyte—macrophage regulators: Reappraisal by gene inactivation, Exp. Haematol. 23: 569–572.Google Scholar
  82. Migliaccio, G., Migliaccio, A. R., Valinsky, J., Langley, K., Zsebo, K., Visser, J. W., and Adamson, J. W., 1991, Stem cell factor induces proliferation and differentiation of highly enriched murine hematopoietic cells, Proc. Natl. Acad. Sci. U.S.A. 88(16): 7420–7424.PubMedCrossRefGoogle Scholar
  83. Miura, O., Miura, Y., Nakamura, N., Quelle, F. W., Witthuhn, B. A., Ihle, J. N., and Aoki, N., 1994, Induction of tyrosine phosphorylation of Vav and expression of Pim-1 correlates with Jak2-mediated growth signaling from the erythropoietin receptor, Blood 84(12): 4135–4142.PubMedGoogle Scholar
  84. Miura, Y., Miura, O., Ihle, J. N., and Aoki, N., 1994, Activation of the mitogen-activated protein kinase pathway by the erythropoietin receptor, J. Biol. Chem. 269 (47): 29962–29969.PubMedGoogle Scholar
  85. Miyajima, A., 1992, Molecular structure of the IL-3, GM-CSF and IL-5 receptors, Int. J. Cell Clon. 10(3): 126–134.CrossRefGoogle Scholar
  86. Miyakawa, Y., Oda, A., Druker, B. J., Kato, T., Miyazaki, H., Handa, M., and Ikeda, Y., 1995, Recombinant thrombopoietin induces rapid tyrosine phosphorylation of Janus kinase 2 and Shc in human blood platelets, Blood 86: 23–27.PubMedGoogle Scholar
  87. Mochizuki, D. Y., Eisenman, J. R., Conlon, P. J., Larsen, A. D., and Tushinski, R. J., 1987, Interleukin 1 regulates hematopoietic activity, a role previously ascribed to hemopoietin 1, Proc. Natl. Acad. Sci. U.S.A. 84 (15): 5267–5271.PubMedCrossRefGoogle Scholar
  88. Noguchi, M., Nakamura, Y., Russell, S. M., Ziegler, S. F., Tsang, M., Cao, X., and Leonard, W. J., 1993, Interleukin-2 receptor gamma chain: A functional component of the interleukin-7 receptor [see comments], Science 262 (5141): 1877–1880.PubMedCrossRefGoogle Scholar
  89. Ogawa, M., 1993, Differentiation and proliferation of hematopoietic stem cells, Blood 81 (11): 2844–2853.PubMedGoogle Scholar
  90. Otsuka, T., Eaves, C. J., Humphries, R. K., Hogge, D. E., and Eaves, A. C., 1991, Lack of evidence for abnormal autocrine ór paracrine mechanisms underlying the uncontrolled proliferation of primitive chronic myeloid leukemia progenitor cells, Leukemia 5 (10): 861–868.PubMedGoogle Scholar
  91. Paquette, R. L., Landaw, E. M., Pierre, R. V., Kahan, J., Lubbert, M., Lazcano, O., Isaac, G., McCormick, F., and Koeffler, H. P., 1993, N-ras mutations are associated with poor prognosis and increased risk of leukemia in myelodysplastic syndrome, Blood 82 (2): 590–599.Google Scholar
  92. Pearson, M. A., Heyworth, C. M., Whetton, A. D., Dexter, T. M., and Owen-Lynch, P. J., 1996, Molecular mechanisms of signal transduction in hematopoietic lineages,in Hemopoietic Cell Lineages (N. G. Testa, B. I. Lord, and T. M. Dexter, eds.), M. Dekker, New York (in press).Google Scholar
  93. Pendergast, A. M., Muller, A. J., Havlik, M. H., Clark, R., McCormick, F., and Witte, O. N., 1991, Evidence for regulation of the human ABL tyrosine kinase by a cellular inhibitor, Proc. Natl. Acad. Sci. U.S.A. 88 (13): 5927–5931.PubMedCrossRefGoogle Scholar
  94. Reedijk, M., Liu, X., van der Geer, P., Letwin, K., Waterfield, M. D., Hunter, T., and Pawson, T., 1992, Tyr 721 regulates specific binding of the CSF-1 receptor kinase insert to PI 3’-kinase SH2 domains: A model for SH2mediated receptor-target interactions, EMBO J. 11 (4): 1365–1372.PubMedGoogle Scholar
  95. Renshaw, M. W., McWhirter, J. R., and Wang, J. Y., 1995, The human leukemia oncogene bcr-abl abrogates the anchorage requirement but not the growth factor requirement for proliferation, Mol. Cell Biol. 15(3): 12861293.Google Scholar
  96. Rettenmier, C. W., and Roussel, M. F., 1988, Differential processing of colony-stimulating factor 1 precursors encoded by two human cDNAs, Mol. Cell Biol. 8 (11): 5026–5034.PubMedGoogle Scholar
  97. Reuther, G. W., Fu, H., Cripe, L. D., Collier, R. J., and Pendergast, A. M., 1994, Association of the protein kinases c–Bcr and Bcr–Abl with proteins of the 14–3–3 family [see comments], Science 266: 129 – 133.PubMedCrossRefGoogle Scholar
  98. Roberts, R., Gallagher, J., Spooncer, E., Allen, T. D.. Bloomfield, F., and Dexter, T. M., 1988, Heparin sulphate bound growth factors: A mechanism for stromal cell mediated hematopoiesis, Nature 332: 376–378.Google Scholar
  99. Rosnet, O., Marchetto, S., deLapeyriere, O., and Birnbaum, D., 1991, Murine Flt3, a gene encoding a novel tyrosine kinase receptor of the PDGFRICSFIR family, Oncogene 6 (9): 1641–1650.PubMedGoogle Scholar
  100. Rossner, M. T., McArthur, G. A., Allen, T. D., and Metcalf, D., 1994, Fms-like tyrosine kinase 3 catalytic domain can transduce a proliferative signal in FDC-Pl cells that is qualitatively similar to the signal delivered by c-Fms, Cell Growth Differ. 5 (5): 549–555.PubMedGoogle Scholar
  101. Rottapel, R., Reedijk, M., Williams, D. E., Lyman, S. D., Anderson, M. D., Pawson, T., and Bernstein, A., 1991, The Steel/W transduction pathway: kit autophosphorylation and its association with a unique subset of cytoplasmic signaling proteins is induced by the Steel factor, Mol. Cell Biol. 11 (6): 3043–3051.PubMedGoogle Scholar
  102. Rottapel, R., Turck, C. W., Casteran, N., Liu, X., Birnbaum, D., Pawson, T., and Dubreuil, P., 1994, Substrate specificities and identification of a putative binding site for PI3K in the carboxy tail of the murine Flt3 receptor tyrosine kinase, Oncogene 9 (6): 1755–1765.PubMedGoogle Scholar
  103. Roussel, M. F., 1994, Signal transduction by the macrophage-colony-stimulating factor receptor (CSF-1R), J. Cell Sci. Suppl. 18 (105): 105–108.PubMedGoogle Scholar
  104. Ruscetti, F. W., Dubois, C. M., Jacobsen, S. E., and Keller, J. R., 1992, Transforming growth factor beta and interleukin-l: A paradigm for opposing regulation of hematopoiesis, Baillieres Clin. Haematol. 5 (3): 703–721.PubMedCrossRefGoogle Scholar
  105. Sattler, M., Durstin, M. A., Frank, D. A., Okuda, K., Kaushansky, K., Ravi, S., and Griffin, J. D., 1995, The thrombopoietin receptor c-MPL activates JAK2 and TYK2 kinases, Exp. Hematol. 23: 1040–1048.PubMedGoogle Scholar
  106. Schmidt, C. A., Oettle, H., Ludwig, W. D., Serke, S., Pawlaczyk, P. B., Wilborn, F., Binder, L. T., Huhn, D., and Siegert, W., 1994, Overexpression of the Raf-1 proto-oncogene in human myeloid leukemia, Leuk. Res. 18 (6): 409–413.PubMedCrossRefGoogle Scholar
  107. Shultz, L. D., Schweitzer, P. A., Rajan, T. V., Yi, T., Ihle, J. N., Matthews, R. J., Thomas, M. L., and Beier, D. R., 1993, Mutations at the murine motheaten locus are within the hematopoietic cell protein-tyrosine phosphatase (Hcph) gene, Cell 73 (7): 1445–1454.PubMedCrossRefGoogle Scholar
  108. Shurtleff, S. A., Downing, J. R., Rock, C. O., Hawkins, S. A., Roussel, M. F., and Sherr, C. J., 1990, Structural features of the colony-stimulating factor 1 receptor that affect its association with phosphatidylinositol 3-kinase, EMBO J. 9 (8): 2415–2421.PubMedGoogle Scholar
  109. Siczkowski, M., Clarke, D., and Gordon, M. Y., 1992, Binding of primitive hematopoietic progenitor cells to marrow stromal cells involves heparin sulfate, Blood 80 (4): 912–917.PubMedGoogle Scholar
  110. Sirard, C., Laneuville, P., and Dick, J. E., 1994, Expression of bcr-abl abrogates factor-dependent growth of human hematopoietic M07E cells by an autocrine mechanism, Blood 83(6): 1575–1585.PubMedGoogle Scholar
  111. Small, D., Levenstein, M., Kim, E., Carow, C., Amin, S., Rockwell, P., Witte, L., Burrow, C., Ratajczak, M. Z., Gewirtz, A. M., and Civin, K. I., 1994, STK-1, the human homolog of Flk-2/Flt-3, is selectively expressed in CD34+ human bone marrow cells and is involved in the proliferation of early progenitor/stem cells, Proc. Natl. Acad. Sci. U.S.A. 91 (2): 459–463.Google Scholar
  112. Sokol, L., Prchal, J. F., D’ Andrea, A., Rado, T. A., and Prchal, J. T., 1994, Mutation in the negative regulatory element of the erythropoietin receptor gene in a case of sporadic primary polycythemia, Exp. Hematol. 22 (5): 447–453.PubMedGoogle Scholar
  113. Spangrude, G. J., 1989, Enrichment of murine hematopoietic stem cells: Diverging roads, Immunol. Today 10(10): 344–350.PubMedCrossRefGoogle Scholar
  114. Spangrude, G. J., Heimfeld, S., and Weissman, I. L., 1988a, Purification and characterization of mouse hemato-poietic stem cells [published erratum appears in Science 1989, 244:1030], Science 241: 58–62.PubMedCrossRefGoogle Scholar
  115. Spangrude, G. J., Muller, S. C., Heimfeld, S., and Weissman, I. L., 1988b, Two rare populations of mouse Thy-llo bone marrow cells repopulate the thymus, J. Exp. Med. 167(5): 1671–1683.PubMedCrossRefGoogle Scholar
  116. Stanley, E. R., Bartocci, A., Patinkin, D., Rosendaal, M., and Bradley, T. R., 1986, Regulation of very primitive, multipotent, hemopoietic cells by hemopoietin-1, Cell 45 (5): 667–672.PubMedCrossRefGoogle Scholar
  117. Stanley, E., Lieschke, G. J., Grail, D., Metcalf, D., Hodgson, G., Gall, J. A., Maher, D. W., Cebon, J., Sinickas, V., and Dunn, A. R., 1994, Granulocyte/macrophage colony-stimulating factor-deficient mice show no major perturbation of hematopoiesis but develop a characteristic pulmonary pathology, Proc. Natl. Acad. Sci. U.S.A. 91 (12): 5592–5596.PubMedCrossRefGoogle Scholar
  118. Tauchi, T., Feng, G. S., Shen, R., Hoatlin, M., Bagby, G. J., Kabat, D., Lu, L., and Broxmeyer, H. E., 1995, Involvement of SH2-containing phosphotyrosine phosphatase Syp in erythropoietin receptor signal transduction pathways, J. Biol. Chem. 270(10): 5631–5635.PubMedCrossRefGoogle Scholar
  119. Taylor, C., McGlynn, H., Carter, G., Baker, A. H., Warren, N., Ridge, S. A., Owen, G., Thompson, E., Thompson, P. W., and Jacobs, A., and Padua, R. A., 1995, RAS and FMS mutations following cytotoxic therapy for childhood acute lymphoblastic leukaemia, Leukemia 9 (3): 466–470.PubMedGoogle Scholar
  120. Terstappen, L. W., Huang, S., Safford, M., Lansdorp, P. M., and Loken, M. R., 1991, Sequential generations of hematopoietic colonies derived from single nonlineage-committed CD34+CD38— progenitor cells, Blood 77 (6): 1218–1227.PubMedGoogle Scholar
  121. Testa, U., Pelosi, E., Gabbianelli, M., Fossati, C., Campisi, S., Isacchi, G., and Peschle, C., 1993, Cascade transactivation of growth factor receptors in early human hematopoiesis, Blood 81 (6): 1442–1456.PubMedGoogle Scholar
  122. Till, J. E., and McCulloch, E. A., 1961, A direct measurement of the radiation sensitivity of normal mouse bone marrow cells, Radiation Res. 14 (213): 383–387.Google Scholar
  123. Tortolani, P. J., Johnston, J. A., Bacon, J. M., McVicar, D. W., Shimosaka, D., Linnekin, D., Longs, D. L., and O’Shea, J. J., 1995, Thrombopoietin induces tyrosine phosphorylation and activation of Janus kinase, JAK2, Blood 85: 3444–3452.PubMedGoogle Scholar
  124. Tsuji, K., Zsebo, K. M., and Ogawa, M., 1991, Enhancement of murine blast cell colony formation in culture by recombinant rat stem cell factor, ligand for c-kit, Blood 78 (5): 1223–1229.PubMedGoogle Scholar
  125. Ullrich, A., and Schlessinger, J., 1990, Signal transduction by receptors with tyrosine kinase activity, Cell 61 (2): 203–212.PubMedCrossRefGoogle Scholar
  126. Van Etten, R. A., Jackson, P., and Baltimore, D., 1989, The mouse type IV c-abl gene product is a nuclear protein, and activation of transforming ability is associated with cytoplasmic localization, Cell 58 (4): 669–678.PubMedCrossRefGoogle Scholar
  127. Van Etten, R. A., Jackson, P. K., Baltimore, D., Sanders, M. C., Matsudaira, P. T., and Janmey, P. A., 1994, The COOH terminus of the c-Abl tyrosine kinase contains distinct F- and G-actin binding domains with bundling activity [published erratum appears in J. Cell Biol. 1994, 124(5):865], J. Cell Biol. 124 (3): 325–340.PubMedCrossRefGoogle Scholar
  128. Varticovski, L., Druker, B., Morrison, D., Cantley, L., and Roberts, T., 1989, The colony stimulating factor-I receptor associates with and activates phosphatidylinositol-3 kinase, Nature 342: 699–678.PubMedCrossRefGoogle Scholar
  129. Visser, J. W., and de Vries, P., 1988, Isolation of spleen-colony forming cells (CFU-s) using wheat germ agglutinin and rhodamine 123 labeling, Blood Cells 14 (2–3): 369–384.PubMedGoogle Scholar
  130. Visser, J. W., and Van Dekkum, D. W., 1990, Purification of pluripotent hemopoietic stem cells: Past and present, Exp. Hematol. 18(3): 248–256.PubMedGoogle Scholar
  131. Vogt, M., Lesley, J., Bogenberger, J. M., Haggblom, C., Swift, S., and Haas, M., 1987, The induction of growth factor-independence in murine myelocytes by oncogenes results in monoclonal cell lines and is correlated with cell crisis and karyotypic instability, Oncogene Res. 2 (1): 49–63.PubMedGoogle Scholar
  132. Wang, J. Y. J., 1992, Modelling chronic myeloid leukemia, Curr. Biol. 2: 70–72.PubMedCrossRefGoogle Scholar
  133. Watowich, S. S., Hilton, D. J., and Lodish, H. F., 1994, Activation and inhibition of erythropoietin receptor function: Role of receptor dimerization, Mol. Cell Biol. 14 (6): 3535–3549.PubMedGoogle Scholar
  134. Welch, P. J., and Wang, J. Y., 1993, A C-terminal protein-binding domain in the retinoblastoma protein regulates nuclear c-Ahl tyrosine kinase in the cell cycle, Cell 75 (4): 779–790.PubMedCrossRefGoogle Scholar
  135. Welham, M. J., and Schrader, J. W., 1992, Steel factor-induced tyrosine phosphorylation in murine mast cells. Common elements withlL-3-induced signal transduction pathways, J. Immunol. 149 (8): 2772–2782.PubMedGoogle Scholar
  136. Whetton, A. D., Heyworth, C. M., Nicholls, S. E., Evans, C. A., Lord, J. M., Dexter, T. M., and Owen-Lynch, P. J., 1994, Cytokine-mediated protein kinase C activation is a signal for lineage determination in bipotential granulocyte macrophage colony-forming cells, J. Cell Biol. 125 (3): 651–659.PubMedCrossRefGoogle Scholar
  137. Wiktor-Jedrzejczak, W., Bartocci, A., Ferrante, A. Jr., Ahmed-Ansari, A., Sell, K. W., Pollard, J. W., and Stanley, E. R., 1990, Total absence of colony-stimulating factor 1 in the macrophage-deficient osteopetrotic (op/op) mouse [published erratum appears in Proc. Natl. Acad. Sci. U.S.A. 1991, 88(13):5937], Proc. Natl. Acad. Sci. U.S.A. 87 (12): 4828–4832.PubMedCrossRefGoogle Scholar
  138. Witte, O. N., 1990, Steel locus defines new multipotent growth factor, Cell 63 (1): 5–6.PubMedCrossRefGoogle Scholar
  139. Yi, T., Mui, A. L., Krystal, G., and Ihle, J. N., 1993, Hematopoietic cell phosphatase associates with the interleukin-3 (IL-3) receptor beta chain and down-regulates IL-3-induced tyrosine phosphorylation and mitogenesis, Mol. Cell Biol. 13 (12): 7577–7586.PubMedGoogle Scholar
  140. Yoder, M. C., and Williams, D.A., 1995, Matrix molecule interactions with the hematopoietic stem cell, Exp. Hematol. 23: 961–967.PubMedGoogle Scholar
  141. Yoshida, H., Hayashi, S., Kunisada, T., Ogawa, M., Nishikawa, S., Okamura, H., Sudo, T., Shultz, L. D., and Nishikawa, S., 1990, The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene, Nature 345: 442–444.PubMedCrossRefGoogle Scholar
  142. Young, J. C., and Witte, O. N., 1988, Selective transformation of primitive lymphoid cells by the bcr/abl oncogene expressed in long term lymphoid or myeloid cultures, Mol. Cell Biol. 8: 4079–4087.PubMedGoogle Scholar
  143. Zeigler, F. C., Bennett, B. D., Jordan, C. T., Spencer, S.D., Baumhueter, S., Carroll, K. J., Hooley, J., Bauer, K., and Matthews, W., I994a, Cellular and molecular characterization of the role of the fik-2/flt-3 receptor tyrosine kinase in hematopoietic stem cells, Blood 84(8):2422–2430.Google Scholar
  144. Zeigler, F. C., de Sauvage, F., Widmer, H. R., Keller, A., Donahue, C., Schreiber, R. D., Malloy, B., Hass, P., Eaton, D., and Matthews, W., 1994b, In vitro megakaryocytopoietic and thrombopoietic activity of c-mpl ligand (TPO) on purified murine hematopoietic stem cells, Blood 84(12): 4045–4052.Google Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Caroline A. Evans
    • 1
  • Andrew Pierce
    • 1
  1. 1.Leukaemia Research Fund Cellular Development Unit, Department of Biochemistry and Applied Molecular BiologyUMISTManchesterUK

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