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Novel primitive lymphoid tumours induced in transgenic mice by cooperation between myc and bcl-2

Nature volume 348, pages 331–333 (1990)Cite this article

Abstract

THE putative oncogene bcl-2 is juxtaposed to the immunoglobulin heavy chain (Igh) locus1-3 by the t(14;18) chromosomal translocation typical of human follicular B-cell lymphomas4. The bcl-2 gene product (refs 5,6) is not altered by the translocation, but its expression is deregulated6–8, presumably by the Igh enhancer Eµ. Constitutive bcl-2 expression seems to augment cell survival, as infection with a bcl-2 retrovirus enables certain growth factor-dependent mouse cell lines to maintain viability when deprived of factor9,10. Furthermore, high levels of the bcl-2 product can protect human B and T lymphoblasts under stress11,12 and thereby confer a growth advantage12–14. Mice expressing a bcl-2 transgene controlled by the Igh enhancer accumulate small non-cycling B cells which survive unusually well in vitro15–17 but do not show a propensity for spontaneous tumorigenesis15,16. In contrast, an analogous myc transgene, designed to mimic the myc–Igh translocation product typical of Burkitt's lymphoma and rodent plasmacytoma18, promotes B lymphoid cell proliferation and predisposes mice to malignancy in pre-B and B lymphoid cells19-22. Previous experiments have suggested that bcl-2 can cooperate with deregulated myc to improve in vitro growth of pre-B and B cells9,11. Here we describe a marked synergy between bcl-2 and myc in doubly transgenic mice. Eµ–bcl–2/myc mice show hyperproliferation of pre-B and B cells and develop tumours much faster than Eµ–myc mice. Surprisingly, the tumours derive from a cell with the hallmarks of a primitive haemopoietic cell, perhaps a lymphoid-committed stem cell.

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Authors and Affiliations

  1. The Walter and Eliza Hall Institute of Medical Research, Post Office, Royal Melbourne Hospital, Victoria, 3050, Australia

    Andreas Strasser, Alan W. Harris, Mary L. Bath & Suzanne Cory

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  1. Andreas Strasser
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  2. Alan W. Harris
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  3. Mary L. Bath
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  4. Suzanne Cory
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Strasser, A., Harris, A., Bath, M. et al. Novel primitive lymphoid tumours induced in transgenic mice by cooperation between myc and bcl-2. Nature 348, 331–333 (1990). https://doi.org/10.1038/348331a0

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