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Mutator phenotype of BCR – ABL transfected Ba/F3 cell lines and its association with enhanced expression of DNA polymerase β

Oncogene volume 18, pages 2676–2680 (1999)Cite this article

Abstract

Chronic myelogenous leukemia (CML) is characterized by the Philadelphia chromosome resulting from the translocation t(9-22) producing the chimeric 190 and 210 kDa BCR – ABL fusion proteins. Evolution of the CML to the more agressive acute myelogenous leukemia (AML) is accompanied by increased cellular proliferation and genomic instability at the cytogenetic level. We hypothezised that genomic instability at the nucleotide level and spontaneous error in DNA replication may also contribute to the evolution of CML to AML. Murine Ba/F3 cell line was transfected with the p190 and p210-encoding BCR – ABL oncogenes, and spontaneous mutation frequency at the Na-K-ATPase and the hypoxanthine guanine phosphoribosyl transferase (HPRT) loci were measured. A significant 3 – 5-fold increase in mutation frequency for the transfected cells relative to the untransfected control cells was found. Furthermore, we observed that BCR – ABL transfection induced an overexpression of DNA polymerase β, the most inaccurate of the mammalian DNA polymerases, as well as an increase in its activity, suggesting that inaccuracy of DNA replication may account for the observed mutator phenotype. These data suggest that the Philadelphia abnormality confers a mutator phenotype and may have implications for the potential role of DNA polymerase β in this process.

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Acknowledgements

This work was supported by La Ligue contre le Cancer – Comité de la Haute-Garonne (grants to YC and JSH). l'Association pour la Recherche sur le Cancer (grant to JSH) and by La Ligue Nationale contre le Cancer (grant to AGT).

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Authors and Affiliations

  1. Institut de Pharmacologie et de Biologie Structurale, UPR CNRS 9062, 205, route de Narbonne, Toulouse cedex, 31077, France

    Y Canitrot, M Fréchet, B Salles, C Cazaux & JS Hoffmann

  2. CJF INSERM 9503, Institut Claudius Régaud, 20 rue du pont St-Pierre, Toulouse, 31052, France

    D Lautier & G Laurent

  3. Institut Gustave Roussy, INSERM U362, 1 rue C. Desmoulins, Villejuif, 94805, cedex, France

    A Ahmed & AG Turhan

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  1. Y Canitrot
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  2. D Lautier
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Canitrot, Y., Lautier, D., Laurent, G. et al. Mutator phenotype of BCR – ABL transfected Ba/F3 cell lines and its association with enhanced expression of DNA polymerase β. Oncogene 18, 2676–2680 (1999). https://doi.org/10.1038/sj.onc.1202619

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