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Animal Models

Suppressed apoptosis of pre-B cells in bone marrow of pre-leukemic p190bcr/abl transgenic mice

Leukemia volume 15, pages 819–827 (2001)Cite this article

Abstract

Mice transgenic for a p190bcr/abl construct develop pre-B cell leukemia/lymphoma, providing a model of Ph+ ALL. To investigate events in tumorigenesis, immunofluorescence labeling, flow cytometry and a short-term culture assay were used to quantitate precursor B cells and their apoptotic rates in bone marrow of p190bcr/abl transgenic mice over a wide age range. Malignancies appeared rapidly at 8–12 weeks of age, followed by slower tumor onset. At 8–12 weeks in normal mice, the apoptotic rate fell among pro-B cells but increased steeply among pre-B cells, while the total number of B lineage cells declined. In contrast, in p190bcr/abl transgenic mice over the same time period, while pro-B cells remained normal in apoptotic rate and number, apoptosis of pre-B cells was markedly inhibited and the number of B lymphocytes increased. At later ages (14–30 weeks), B cell precursors in control mice remained constant in apoptotic activity and number, while in the few surviving transgenic mice B cell populations were expanded. The results reveal characteristic changes in apoptotic activity among B cell precursors in bone marrow during early life, severely perturbed in preleukemic p190bcr/abl transgenic mice by a preferential suppression of pre-B cell apoptosis. p190bcr/abl may thus promote leukemogenesis by permitting aberrant cells generated during early B cell development to evade a normal quality checkpoint and negative selection.

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Acknowledgements

This work was supported by grants from the Medical Research Council of Canada and the National Cancer Institute of Canada with funds from the Canadian Cancer Society.

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada

    Q Yu & DG Osmond

  2. Departments of Medicine and Oncology, McGill University, Montreal, Quebec, Canada

    J Brain & P Laneuville

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  1. Q Yu
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  2. J Brain
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  3. P Laneuville
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  4. DG Osmond
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Yu, Q., Brain, J., Laneuville, P. et al. Suppressed apoptosis of pre-B cells in bone marrow of pre-leukemic p190bcr/abl transgenic mice. Leukemia 15, 819–827 (2001). https://doi.org/10.1038/sj.leu.2402079

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  • DOI: https://doi.org/10.1038/sj.leu.2402079

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