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Translocation of c-abl oncogene correlates with the presence of a Philadelphia chromosome in chronic myelocytic leukaemia

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Abstract

The localization of cellular oncogenes near the break points of tumour-specific chromosomal aberrations suggests an involvement of these genes in the generation of neoplasms1,2. Recently, we demonstrated3 the translocation of the human cellular homologue (c-abl) of the transforming sequence of Abelson murine leukaemia virus (A-MuLV) from chromosome 9 to the Philadelphia chromosome (Ph1) in chronic myelocytic leukaemia (CML). In an attempt to investigate the significance of this translocation in the pathogenesis of CML, we have now studied two CML patients with complex translations, t(9; 11; 22) and t(1; 9; 22), and two CML Ph1-negative patients with apparently normal karyotypes. In addition to using blot hybridization with human c-abl probes and DNA from Rodent: CML cell hybrids as before, we have used in situ hybridization of these probes directly to metaphase chromosomes of CML patients. These studies show that the c-abl gene is translocated in Ph1-positive but not in Ph1-negative CML patients. CML without the Ph1 chromosome seems to be a distince entity with a different origin, and this view is supported by clinical observations including correlations which reveal a poorer prognosis4,5.

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Authors and Affiliations

  1. Department of Cell Biology and Genetics, Erasmus University, PO Box 1738, Rotterdam, 3000 DR, The Netherlands

    Claus R. Bartram, Annelies de Klein, Anne Hagemeijer, Ton van Agthoven, Ad Geurts van Kessel, Dirk Bootsma & Gerard Grosveld

  2. Duncan Guthrie Institute of Medical Genetics, Yorkhill, Glasgow, G3 8SJ, UK

    Malcolm A. Ferguson-Smith, Teresa Davies & Marion Stone

  3. Laboratory of Viral Carcinogenesis, National Cancer Institute, FCRF, Frederick, Maryland, 21791, USA

    Nora Heisterkamp, John R. Stephenson & John Groffen  

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  1. Claus R. Bartram
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  2. Annelies de Klein
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  3. Anne Hagemeijer
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  4. Ton van Agthoven
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  5. Ad Geurts van Kessel
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  6. Dirk Bootsma
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  7. Gerard Grosveld
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  8. Malcolm A. Ferguson-Smith
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  9. Teresa Davies
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  10. Marion Stone
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  11. Nora Heisterkamp
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  12. John R. Stephenson
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  13. John Groffen  
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Bartram, C., de Klein, A., Hagemeijer, A. et al. Translocation of c-abl oncogene correlates with the presence of a Philadelphia chromosome in chronic myelocytic leukaemia. Nature 306, 277–280 (1983). https://doi.org/10.1038/306277a0

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