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Early events in leukemogenesis in P190Bcr-abl transgenic mice

Oncogene volume 19, pages 4362–4374 (2000)Cite this article

Abstract

The activated tyrosine kinase, Bcr-abl, is implicated in a number of hematopoietic malignancies. The exact biological mechanism by which the kinases transforms cells is still not well delineated. Previous data has suggested that the inhibition of apoptosis and the deregulation of cell cycle progression as the result of P210Bcr-abl expression might contribute to leukemogenesis. In vitro systems in which Bcr-Abl is over-expressed have concluded that similar growth regulatory pathways are affected as a result of the expression of both P210 and P190Bcr-abl. Here, we utilized an in vitro P190Bcr-abl leukemia mouse model to dissect the early events that contribute to transformation by this isoform of Bcr-Abl. In this mouse model P190Bcr-abl is expressed as a low but physiologically relevant level in that all mice develop pre-B leukemia lymphomas. We show that cell cycle and apoptotic responses to DNA damage are intact in bone marrow and spleen cells of such animals. We also demonstrate a normal induction of p21WAF-1/CIP1 in both hematopoietic and non-hematopoietic tissue as a result of genotoxic stress. We suggest that P190Bcr-abl induced transformation is different than that of P210Bcr-abl.

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Acknowledgements

We thank Giovana Micelli, Ken McDonald, and Brigitte Goulet for their expert technical assistance, Dr Allan Peterson for facilitating mouse colony establishment, and Dr Bert Vogelstein for the Waf-1 probe. This work was supported by an MRC grant (MT 13253) to P Laneuville. HF Salloukh was supported by student scholarships from the Cedar Cancer Institute and the Royal Victoria Hospital Kauffman Memorial. J Groffen and N Heisterkamp were supported by PHS NIH grants CA47456 and CA50248.

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Authors and Affiliations

  1. Department of Medicine, Division of Experimental Medicine, Royal Victoria Hospital, Hersey Pavilion (H5.21), 687 Pine Avenue West, Montreal, H3A 1A1, Quebec, Canada

    Hashem F Salloukh & Pierre Laneuville

  2. Molecular Oncology Group, Royal Victoria Hospital, Hersey Pavilion (H5.21), 687 Pine Avenue West, Montreal, H3A 1A1, Quebec, Canada

    Hashem F Salloukh, Ian Vowles & Pierre Laneuville

  3. Division of Hematology/Oncology, Section of Molecular Diagnosis, Children's Hospital of Los Angeles, 4650 Sunset Boulevard, Los Angeles, 90027, California, CA, USA

    Nora Heisterkamp & John Groffen

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  1. Hashem F Salloukh
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Salloukh, H., Vowles, I., Heisterkamp, N. et al. Early events in leukemogenesis in P190Bcr-abl transgenic mice. Oncogene 19, 4362–4374 (2000). https://doi.org/10.1038/sj.onc.1203804

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