Abstract
Chronic myelogenous leukemia (CML) is a malignancy of the pluripotent hematopoietic stem cell. This disease accounts for 15–20% of all leukemias with an annual incidence of between 1 to 2 cases per 100,000 persons per year. The median age of onset is approximately 50 years of age. Clinically, the disease is characterized by a chronic phase in which the only apparent abnormality is the massive expansion of functionally normal myeloid lineage cells 1. During this chronic phase, myeloid cells retain the capacity to differentiate normally. Following an average chronic phase duration of about three years, the disease transforms to an accelerated or blast phase in which there is a progressive loss of the capacity for terminal differentiation of myeloid lineage cells along with the accumulation of cytogenetic abnormalities 1.
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References
B. Clarkson, The chronic leukemias. In: J.B. Wyngaarden and L.H. Smiths, Jr. (eds): Cecil Textbook of Medicine, 18th Edition, W. B. Saunders, Philadelphia, p. 988–1001 (1988)
H.M. Kantarjian, A.B. Deisseroth, R. Kurzrock, Z. Estrov and M. Talpaz, Chronic myelogenous leukemia: a concise update. Blood. 82: 691–703 (1993)
J.M. Goldman, Management of chronic myeloid leukaemia. Blood REv. 8: 21–29 (1994)
The Italian Cooperative Study Group on Chronic Myeloid Leukemia, Interferon alfa-2a as compared with conventional chemotherapy for the treatment of chronic myeloid leukemia. N Engl J Med. 330: 820–825 (1994)
R. Hehlmann, H. HeimpeI, J. Hasford, H.J. Kolb, H. Pralle, D.K. Hossfeld, W. Queisser, H. Loffler, A. Hochhau and B. Heinze, et. al., Randomized comparison of interferon-alpha with busulfan and hydroxyurea in chronic myelogenous leukemia. The German CML Study Group. Blood. 84: 4064–4067 (1994)
S.G. O’Brien and J.M. Goldman, Autografting in chronic myeloid leukaemia. Blood Rev. 8: 63–69 (1994)
P.B. McGlave, R De-Fabritiis, A. Deisseroth, J. Goldman, M. Barnett, J. Reiffers, B. Simonsson, A. Carella and D. Aeppli, Autologous transplants for chronic myelogenous leukaemia: results from eight transplant groups. Lancet. 343: 1486–1488 (1994)
P.C. Nowell and D.A. Hungerford, A minute chromosome in human chronic granulocytic leukemia. Science. 132: 1497–1501 (1960)
J.D. Rowley, A new consistent abnormality in chronic myelogenous leukaemia identified by quinacrine, fluorescence and giemsa staining. Nature. 243: 290–293 (1973)
N. Heisterkamp, J.R. Stephenson, J. Groffen, P.F. Hansen, A. de Klein, C.R. Bartram and G. Grosveld, Localization of the c-abl oncogene adjacent to a translocation break point in chronic myelocytic leukemia. Nature. 306: 239–242 (1983)
C.R. Bartram, A. de Klein, A. Hagemeijer, T. van Agthoven, A. Geurts von Kessel, D. Bootsma, G. Gros-veld, M.A. Ferguson-Smith, T. Davies, M. Stone, N. Heisterkamp, J.R. Stephenson and J. Groffen, Translocation of c-abl correlates with the presence of a Philadelphia chromosome in chronic myelocytic leukemia. Nature. 306: 277–280 (1983)
M. Nitta, Y. Kato, A. Strife, M. Wachter, J. Fried, A. Perez, S. Jhanwar, R. Duigou-Osterndorf, R.S.K. Chaganti and B. Clarkson, Incidence of involvement of the B and T lymphocyte lineages in chronic myelogenous leukemia. Blood. 66: 1053–1061 (1985)
C.M. Morris, A.E. Reeve, P.H. Fitzgerald, P.E. Hollings, M.E. Beard and D.C. Heaton, Genomic diversity correlates with clinical variation in Ph’-negative chronic myeloid leukaemia. Nature. 320: 281–283 (1986)
R. Kurzrock, M.B. Blick, M. Talpaz, W.S. Velasquez, J.M. Trujillo, N.M. Kouttab, W.S. Kloetzer, R.B. Arlinghaus and J.U. Gutterman, Rearrangement in the breakpoint cluster region and the clinical course in Philadelphia-negative chronic myelogenous leukemia. Ann Intern Med. 105: 673–679 (1986)
E. Shtivelman, B. Lifshitz, R.P. Gale and E. Canaani, Fused transcript of abl and bcr genes in chronic myelogenous leukaemia. Nature. 315: 550–554 (1985)
Y. Ben-Neriah, G.Q. Daley, A.-M. Mes-Masson, O.N. Witte and D. Baltimore, The chronic myelogenous leukemia-specific P210 protein is the product of the bcr/abl hybrid gene. Science. 233: 212–214 (1986)
R. Kurzrock, J.U. Gutterman and M. Talpaz, The molecular genetics of Philadelphia chromosome-positive leukemias. N Engl J Med. 319: 990–998 (1988)
S.A. Cannistra, Chronic myelogenous leukemia as a model for the genetic basis of cancer. Hematol Oncol Clin North Am. 4: 337–357 (1990)
A. Hermans, N. Heisterkamp, M. von Lindern, S. van Baal, D. Meijer, D. van der Plas, L.M. Wiedemann, J. Groffen, D. Bootsma and G. Grosveld, Unique fusion of bcr and c-abl genes in Philadelphia chromosome positive acute lymphoblastic leukemia. Cell. 51: 33–40 (1987)
S.S. Clark, J. McLaughlin, M. Timmons, A.M. Pendergast, Y. Ben-Neriah, L.W. Dow, W. Crist, G. Rovera, S.D. Smith and O.N. Witte, Expression of a distinctive BCR-ABL oncogene in Phl-positive acute lymphocytic leukemia (ALL). Science. 775–777 (1988)
T.G. Lugo, A.M. Pendergast, A.J. Muller and O.N. Witte, Tyrosine kinase activity and transformation potency of bcr-abl oncogene products. Science. 247: 1079–1082 (1990)
G.Q. Daley and D. Baltimore, Transformation of an interleukin 3-dependent hematopoietic cell line by the chronic myelogenous leukemia-specific P210bcr/abl protein. Proc Natl Acad Sci USA. 85: 9312–9316 (1988)
J.B. Konopka, S.M. Watanabe and O.N. Witte, An alteration of the human c-abl protein in K562 unmasks associated tyrosine kinase activity. Cell. 37: 1035–1042 (1984)
J. McLaughlin, E. Chianese and O.N. Witte, In vitro transformation of immature hematopoietic cells by the P210 BCR/ABL oncogene product of the Philadelphia chromosome. Proc Natl Acad Sci USA. 84: 6558–6562 (1987)
G.Q. Daley, R.A. Van Etten and D. Baltimore, Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome. Science. 247: 824–830 (1990)
M.A. Kelliher, J. McLaughlin, O.N. Witte and N. Rosenberg, Induction of a chronic myelogenous leukemia-like syndrome in mice with v-abl and BCR/ABL. Proc Natl Acad Sci USA. 87: 6649–6653 (1990)
M.L. Gishizky, J. Johnson-White and O.N. Witte, Efficient transplantation of BCR-ABL-induced chronic myelogenous leukemia-like syndrome in mice. Proc Natl Acad Sci USA. 90: 3755–3759 (1993)
J.R. McWhirter and J.Y.J. Wang, Activation of tyrosine kinase and microfilament-binding functions of cabl by bcr sequences in bcr/abl fusion proteins. Mol Cell Biol. 11: 1553–1565 (1991)
A.J. Muller, J.C. Young, A.M. Pendergast, M. Pondel, N.R. Landau, D.R. Littman and O.N. Witte. BCR first exon sequences specifically activate the BCR/ABL tyrosine kinase oncogene of Philadelphia chromosome-positive human leukemias. Mol Cell Biol. 11: 1785–1792 (1991)
T. Oda, S. Tamura and B.J. Druker, The SH2 domain of Abl is not required for factor independent growth induced by Bcr-Abl in a murine myeloid cell line. Leukemia. 9: 295–301 (1995)
E. Buchdunger, J. Zimmermann, H. Mett, T. Meyer, M. Muller, U. Regenass and N.B. Lydon, Selective inhibition of the platelet-derived growth factor signal transduction pathway by a protein-tyrosine kinase inhibitor of the 2-phenylaminopyrimidine class. Proc Natl Acad Sci USA. 92: 2558–2562 (1995)
B.J. Druker, S. Tamura, E. Buchdunger, S. Ohno, G.M. Segal, J. Zimmermann and N.B. Lydon, Effects of a selective inhibitor of the ABL tyrosine kinase on the growth of BCR-ABL positive cells. Submitted(1995)
J.S. Greenberger, M.A. Sakakeeny, R.K. Humphries, C.J. Eaves and R.J. Eckner, Demonstration of permanent factor-dependent multipotential (erythroid/neutrophil/basophil) hematopoietic progenitor cell lines. Proc Natl Acad Sci USA. 80: 2391–2395 (1983)
G.C. Avanzi, P. Lista, B. Giovinazzo, R. Miniero, G. Saglio, G. Benetton, R. Coda, G. Cattoretti and L. Pegoraro, Selective growth response to IL-3 of a human leukaemic cell line with megakaryoblastic features. Br Haematol. 69: 359–366 (1988)
T. Matsuguchi, R. Salgia, M. Hallek, M. Eder, B. Druker, T. Ernst and J.D. Griffin, SHC phosphorylation in myeloid cells is regulated by GM-CSF, IL-3, and steel factor and is constitutively increased by p210BCR-ABL. J Biol Chem. 269: 5016–5021. (1994)
U. Matulonis, R. Salgia, K. Okuda, B. Druker and J.D. Griffin, IL-3 and p210BCR/ABL activate both unique and overlapping pathways of signal transduction in a factor-dependent myeloid cell line. Exp Hematol. 21: 1460–1466 (1993)
Y. Kanakura, B. Druker, S.A. Cannistra, Y. Furukawa, Y. Torimoto and J.D. Griffin, Signal transduction of the human granulocyte-macrophage colony-stimulating factor and interleukin-3 receptors involves a common set of cytoplasmic proteins. Blood. 76: 706–715 (1990)
S. Tamura, S. Ohno, E. Buchdunger, J. Zimmermann, N.B. Lydon and B.J. Druker, A selective ABL protein tyrosine kinase inhibitor with potent activity against BCR-ABL positive cells. Submitted(1995)
B.D. Evans, I.E. Smith, A.J. Shorthouse and J.L. Millar, A comparison of the response of human lung carcinoma xenografts to vindesine and vincristine. BrJCancer45: 466–468 (1982)
G.M. Segal, R.E. Magenis, M. Brown, W. Keeble, T.D. Smith, M.C. Heinrich and G.C. Bagby, Repression of Fanconi anemia gene (FACC) expression inhibits growth of hematopoietic progenitor cells. J Clin Invest. 94: 846–852 (1994)
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Druker, B.J., Ohno, S., Buchdunger, E., Tamura, S., Zimmermann, J., Lydon, N.B. (1996). Selective Killing of BCR-ABL Positive Cells with a Specific Inhibitor of the ABL Tyrosine Kinase. In: Mihich, E., Housman, D. (eds) Cancer Genes. Pezcoller Foundation Symposia, vol 7. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5895-8_16
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DOI: https://doi.org/10.1007/978-1-4615-5895-8_16
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