Abstract
The close association of specific chromosome abnormalities with particular types of human cancer has been established by a number of investigators during the past decade [1–6]. A few of the genes involved in consistent chromosome rearrangements, notably translocations, have already been identified, and it is likely that the identity of most of the genes affected by these aberrations will be determined within the next decade. Moreover, for several of the rearrangements, some of the changes in gene structure and function have been defined. Therefore, some general principles that may be applicable to many chromosome rearrangements in human malignant disease are beginning to emerge. Chronic myeloid leukemia (CML) provides one of the clearest examples of our progress in first identifying a recurring chromosome abnormality and then cloning the genes involved in the abnormality. The analysis of these genes and their alteration as a result of the chromosome change is the subject of this lecture.
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References
Mitelman F (1988) Catalog of chromosome aberrations in cancer: Liss, New York
Heim S, Mitelman F (1987) Cancer cytogenetics. Liss, New York
Rowley JD (1988) Chromosome abnormalities in leukemia. J Clin Oncol 6: 194–202
Rowley JD, Testa JR (1983) Chromosome abnormalities in malignant hematologic diseases. In: Advances in cancer research, Academic, New York, pp 103–148
Bloomfield CD, Trent JM, Van den Berghe H (1987) Report of the committee on structural chromosome changes in neoplasia (HGM9). Cytogenet Cell Genet 46: 344–366
Yunis JJ (1983) The chromosomal basis of human neoplasia. Science 221: 227–236
Nowell PC, Hungerford DA (1960) A minute chromosome in human granulocytic leukemia. Science 132: 1497
Rowley JD (1973) A new consistent chromosomal abnormality in chronic myelogenous leukemia. Nature 243: 290–293
De Klein A, Van Kessel AG, Grosveld G et al. (1982) A cellular oncogene is translocated to the Philadelphia chromosome in chronic myelocytic leukemia. Nature 300: 765–767
De Klein A, Hagemeijer A (1984) Cytogenetic and molecular analysis of the Ph1 translocation in chronic myeloid leukemia. Cancer Surv 3: 515–529
Bakhshi A, Minowada J, Arnold A et al. (1983) Lymphoid blast crises of chronic myelogenous leukemia represent stages in the development of B-cell precursors. N Engl J Med 309: 826–831
Whang-Peng J, Canellos GP, Carbone PP et al. (1968) Clinical implications of cytogenetic variants in chronic myelocytic leukemia ( CML ). Blood 32: 755–766
Pugh WC, Pearson M, Vardiman JW et al. (1985) Philadelphia chromosome-negative chronic myelogenous leukaemia: a morphologic reassessment. Br J Haematol 60: 457–467
Morris CM, Reeve AE, Fitzgerald PH et al. (1986) Genomic diversity correlates with clinical variation in Ph1-negative chronic myeloid leukemia. Nature 320: 281–283
Bartram CR (1988) Molecular genetic analyses of chronic myelocytic leukemia. In: Huhn D, Hellriegel KP, Niederle N (eds) Chronic myelocytic leukemia and interferon. Springer, Berlin Heidelberg New York
Groffen J, Stevenson JR, Heisterkamp N et al. (1984) Philadelphia chromosomal breakpoints are clustered within a limited region, bcr, on chromosome 22. Cell 36: 93–99
Westbrook CA, Rubin CM, Carrino JJ et al. (1988) Long-range mapping of the Philadelphia chromosome by pulsed-field gel electrophoresis. Blood 79: 697–702
Konopka JB, Watanabe SM, Witte ON (1984) An alteration of the human c-abl protein in K562 leukemia cells unmasks associate tyrosine kinase activity. Cell 37: 1035–1042
Shtivelman E, Lifshitz B, Gale RP et al. (1985) Fused transcript of abl and bcr genes in chronic myelogenous leukaemia. Nature 315: 550–554
Third international workshop on chromosomes in leukemia (1982). Cancer Genet Cytogenet 4: 95–142
De Klein A, Hagemeijer A, Bartram CR et al. (1986) Rearrangement and translocation of the c-abl oncogene in Philadelphia positive acute lymphoblastic leukemia. Blood 68: 1369–1375
Rubin CM, Carrino JJ, Dickler MN et al. (1988) Heterogeneity of genomic fusion of BCR and ABL in Philadelphia chromosome-positive acute lymphoblastic leukemia. Proc Natl Acad Sci USA 85: 2795–2799
Clark SS, McLaughlin J, Christ WM et al. (1987) Unique forms of the abl tyrosine kinase distinguish Ph1-positive CML from Ph1-positive ALL. Science 235: 85–88
Chan LC, Karhi KK, Rayter SI et al. (1987) A novel abl protein expressed in Philadelphia chromosome positive acute lymphoblastic leukaemia. Nature 325: 635–637
Hooberman A, Carrino JJ, Leibowitz D et al. (1989) Unexpected heterogeneity of BcR-ABL fusion mRNA detected by polymerase chain reaction in Philadelphia chromosome acute lymphoblastic leukemia. Proc Natl Acad Sci USA 86: 4259–4263
Nomiyama H, Fromental C, Xiao JH et al. (1987) Cell-specific activity of the constituent elements of the simian virus 40 enhancer. Proc Natl Acad Sci USA 84: 7881–7885
Leder P, Battey J, Lenoir G et al. (1983) Translocations among antibody genes in human cancer. Science 222: 765–771
Croce CM, Isobe M, Palumbo A etal. (1985) Gene for α-chain of human T-cell receptor: location on chromosome 14 region involved in T-cell neoplasms. Science 227: 1044–1047
Shima EA, Le Beau MM, McKeithan TW et al. (1986) Gene encoding the α-chain of the T-cell receptor is moved immediately downstream of c-myc in a chromosomal 8; 14 translocation in a cell line from a human T-cell leukemia. Proc Natl Acad Sci USA 83: 3439–3443
Mathieu-Mahul D, Caubet JF, Bernheim A et al. (1985) Molecular cloning of a DNA fragment from human chromosome 14 (14ql 1) involved in T cell malignancies. EMBO J 4: 3427–3433
Lang RA, Metealf D, Gough NM etal. (1985) Expression of a hemopoietic growth factor cDNA in a factor-dependent cell line results in autonomous growth and tumorigenicity. Cell 43: 531–542
Bishop JM (1987) The molecular genetics of cancer. Science 235: 305–311
Duesberg PH (1987) Retroviruses as carcinogens and pathogens: expectations and reality. Cancer Res 47: 1199–1220
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Rowley, J.D. (1989). Molecular Analysis of Rearrangements in Philadelphia (Ph1) Chromosome-Positive Leukemia. In: Neth, R., et al. Modern Trends in Human Leukemia VIII. Haematology and Blood Transfusion / Hämatologie und Bluttransfusion, vol 32. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-74621-5_1
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DOI: https://doi.org/10.1007/978-3-642-74621-5_1
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