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  • Original Paper
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T-cell lymphomas mask slower developing B-lymphoid and myeloid tumours in transgenic mice with broad haemopoietic expression of MYC

Oncogene volume 24, pages 3544–3553 (2005)Cite this article

Abstract

Deregulation of MYC expression occurs in many haematological malignancies. Previous studies modelling MYC-induced lymphomagenesis in the mouse used transgenic vectors that directed MYC overexpression in a lineage-specific manner. Here, we describe a transgenic mouse strain in which constitutive MYC expression is driven broadly in haemopoiesis by a vector containing regulatory elements of the Vav gene. Healthy young VavP-MYC17 mice had multiple haemopoietic abnormalities, most notably increased size and numbers of B-lymphoid cells, monocytes and megakaryocytes. The mice rapidly developed tumours and, surprisingly, these were exclusively T-cell lymphomas, mostly of mature CD4+ CD8− T cells, a tumour type that is seldom seen in mouse models. To examine tumour development in the absence of the susceptible T cells, we bred VavP-MYC17 mice lacking the Rag1 recombinase. They survived longer and succumbed to tumours of several different haemopoietic cell types: pre-T cells, pro-B cells, macrophages and unusual progenitor cells. Thus, although T-lineage cells have the shortest latent period to transformation, the VavP-MYC17 transgene drives malignant transformation of multiple cell types and VavP-MYC17 mice provide a new model for tumours of multiple haemopoietic lineages.

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Acknowledgements

We thank J Adams for helpful discussions, A Strasser for his gift of antibodies, A Wiegmans for technical assistance, C Young for cell sorting, S Mihajlovic for histological processing, and K Birchall and A Naughton for animal husbandry. This work was supported by the National Health and Medical Research Council (NHMRC, Canberra, Program Grant 257502), the US National Cancer Institute (Grant CA43540) and the Leukemia and Lymphoma Society (New York, Specialized Center of Research Grant 7015).

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  1. The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, Victoria, 3050, Australia

    Darrin P Smith, Mary L Bath, Alan W Harris & Suzanne Cory

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  1. Darrin P Smith
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Correspondence to Suzanne Cory.

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Smith, D., Bath, M., Harris, A. et al. T-cell lymphomas mask slower developing B-lymphoid and myeloid tumours in transgenic mice with broad haemopoietic expression of MYC. Oncogene 24, 3544–3553 (2005). https://doi.org/10.1038/sj.onc.1208399

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