Abstract
AKXD recombinant inbred mice develop a variety of leukemias and lymphomas due to retrovirally mediated insertional activation of cellular proto-oncogenes. We describe a new retroviral insertion site that is the most frequent genetic alteration in AKXD B-cell leukemias. Multiple genes flank the site of viral insertion, but the expression of just two, Hex and mEg5, is significantly upregulated. Hex is a divergent homeobox gene that is transiently expressed in many hematopoietic lineages, suggesting an involvement in cellular differentiation. mEg5 is a member of the bim-C subfamily of kinesin related proteins that are necessary for spindle formation and stabilization during mitosis. Our data provide the first genetic evidence for the activation of these genes in leukemia, and suggest that unscheduled expression of Hex and mEg5 contributes to the development of B-cell leukemia. In addition, this work highlights the use of genomic approaches for the study of position effect mutations.
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Acknowledgements
We thank Alka Malhotra for help with constructing the BAC 542i7 library, Toni Jago for help with tumor tissue collection, and Loren Hauser and Richard Mural for helpful discussions of this work. We are grateful to Allan Bradley and Richard Behringer for critical reading of the manuscript. This work is supported by a grant from the National Cancer Institute (R29CA63229), and by an American Cancer Society Junior Faculty Research Award (JFRA0553) to MJ Justice.
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Hansen, G., Justice, M. Activation of Hex and mEg5 by retroviral insertion may contribute to mouse B-cell leukemia. Oncogene 18, 6531–6539 (1999). https://doi.org/10.1038/sj.onc.1203023
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DOI: https://doi.org/10.1038/sj.onc.1203023
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