T-cell lymphomas mask slower developing B-lymphoid and myeloid tumours in transgenic mice with broad haemopoietic expression of MYC
- Author(s)
- Smith, DP; Bath, ML; Harris, AW; Cory, S;
- Details
- Publication Year 2005-05-19,Volume 24,Issue #22,Page 3544-3553
- Journal Title
- ONCOGENE
- Publication Type
- Journal 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.
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- C-MYC; RAG-1-DEFICIENT MICE; MOUSE; DIFFERENTIATION; MUTATIONS; APOPTOSIS; LEUKEMIA; BCL-2; CHEMORESISTANCE; CLASSIFICATION
- Publisher's Version
- https://doi.org/10.1038/sj.onc.1208399
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2005-05-19 12:00:00