Abstract
Interferons (IFNs) comprise a heterogenous group of cytokines with pleiotropic activities. The mode of action of IFNs in human disease is still poorly understood. In particular it is not established whether IFNs exert their antineoplastic activity by direct interaction with tumor cells or indirectly by enhancing host antitumor responses. Nor is it known which biological features of a tumor and which host factors determine the sensitivity of malignant diseases to IFN therapy. In order to select IFN-α-sensitive tumor patients we have chosen Philadelphia chromosome- (Ph1)-positive chronic myelocytic leukemia (CML) as a model disease.
This work was financially supported by the Austrian Funds Zur Förderung der wissenschaflichen Forschung, project no. 6526.
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References
Broxmeyer HE, Lu L, Platzer E, Feit C, Juliano L, Rubin BY (1983) Comparative analysis of the influences of human gamma, alpha and beta-interferons on human multipotential (CFU-GEMM), erythroid (BFU-E) and granulocyte-macrophage (CFU-GM) progenitor cells. J Immunol 131:1300–1305
Calabretta B, Venturetti D, Kaczmarek L, Narni F, Talpaz M, Anderson B, Beran M, Baserga R (1986) Altered expression of G1-specific genes in human malignant myeloid cells. Proc Natl Acad Sci USA 83:1495–1498
Carlo-Stella C, Cazzola M, Ganser A, Bergamaschi G, Pedrazzoli P, Hoelzer D, Ascari E (1988) Synergistic antiproliferative effect of recombinant interferon-gamma with recombinant interferon-alpha on chronic myelogenous progenitor cells (CFU-GEMM, CFU-Mk, BFU-E, and CFU-GM). Blood 72:1293–1299
Einat M, Resnitzky D, Kimchi A (1985) Close link between reduction of c-myc expression by interferon and Go/G1 arrest. Nature 313:597–600
Ferrari S, Narni F, Mars W, Kaczmarek L, Venturetti D, Anderson B, Calabretta B (1986) Expression of growth-regulated genes in human acute leukemias. Cancer Res 46:5162–5166
Gastl G, Aulitzky W, Tilg H, Huber H, Hausmaninger H, Seewann HL, Coser C, Prinoth P, Huber C (1987) Dose-related effectiveness of alpha-interferon in chronic myelogenous leukemia. Blut 54:251–252
Geissler D, Lu L, Bruno E, Yang HH, Broxmeyer HE, Hoffman R (1986) The influence of T lymphocyte subsets and humoral factors on colony formation by human bone marrow and blood megakaryocyte progenitor cells in vitro. J Immunol 137: 2508–2513
Greenberg PL, Mosney SA (1987) Cytotoxic effect of interferon in vitro on granulocytic progenitor cells. Cancer Res 37:1794–1799
Kelly K, Siebenlist U (1985) The role of c-myc in the proliferation of normal and malignant cells. J Clin Immunol 5:65–77
Konwalinka G, Geissler D, Peschel Ch, Tomaschek B, Schmalzl F, Huber H, Odavic R, Braunsteiner H (1982) A microagar culture system for cloning human erythropoietic progenitors. Exp Hematol 10:71–76
Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning. A laboratory manual, 2nd edn. Cold Spring Harbor Laboratory Press, Cold Spring Harbor
Niederle N, Kloke O, Osieka R, Wandl U, Opalka B, Schmidt CG (1987) Interferon-alpha2b in the treatment of chronic myelogenous leukemia. Semin Oncol 14 (Suppl 2):29–35
Oladipupo-Williams CK, Svet-Moldavskaya I, Vilcek J, Ohnuma T, Holland JF (1981) Inhibitory effects of human leukocyte and fibroblast interferons on normal and chronic myelogenous leukemia granulocytic progenitor cells. Oncology 38:356–360
Talpaz M, Kantarjian HM, McCredie K, Trujillo JM, Keating MJ, Gutterman JU (1986) Hematologic remission and cytogenetic improvement induced by recombinant human interferon-alpha in chronic myelogenous leukemia. N Engl J Med 314: 1065–1069
Talpaz M, Kantarjian HM, McCredie KB, Keating MJ, Trujillo J, Gutterman (1987) Clinical investigation of human alpha interferon in chronic myelogenous leukemia. Blood 69:1280–1288
Zarling JM, Eskra L, Borden EC, Horoszewicz J, Carter WA (1979) Activation of human natural killer cells cytotoxic for human leukemic cells by purified interferon. J Immunol 123:63–70
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© 1993 Springer-Verlag Berlin Heidelberg
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Gastl, G. et al. (1993). Strategies for Optimizing Cytokine Treatment of Malignancies: Determination of Interferon Sensitivity in Chronic Myelocytic Leukemia. In: Fleischer, J. (eds) Leukemias. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-77083-8_24
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DOI: https://doi.org/10.1007/978-3-642-77083-8_24
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