1. T-cell lymphomas mask slower developing B-lymphoid and myeloid tumours in transgenic mice with broad haemopoietic expression of MYC.
- Author
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Smith DP, Bath ML, Harris AW, and Cory S
- Subjects
- Animals, B-Lymphocytes pathology, B-Lymphocytes physiology, Blotting, Western, Cell Lineage, Disease Models, Animal, Flow Cytometry, Genetic Vectors, Hematologic Neoplasms genetics, Hematologic Neoplasms pathology, Humans, Lymphoma, T-Cell genetics, Megakaryocytes pathology, Megakaryocytes physiology, Mice, Mice, Transgenic, Monocytes pathology, Monocytes physiology, Myeloid Cells physiology, Proto-Oncogene Proteins c-myc genetics, Simian virus 40, Transgenes, Cell Transformation, Neoplastic, Lymphoma, T-Cell pathology, Myeloid Cells pathology, Proto-Oncogene Proteins c-myc metabolism
- 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.
- Published
- 2005
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