T-cell lymphomas mask slower developing B-lymphoid and myeloid tumours in transgenic mice with broad haemopoietic expression of MYC.
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.
Smith
Darrin P
DP
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, Victoria 3050, Australia.
Bath
Mary L
ML
Harris
Alan W
AW
Cory
Suzanne
S
D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology / Q000502:physiology; D015153:Blotting, Western; D019070:Cell Lineage; D002471:Cell Transformation, Neoplastic; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005822:Genetic Vectors; D019337:Hematologic Neoplasms / Q000235:genetics / Q000473:pathology; D006801:Humans; D016399:Lymphoma, T-Cell / Q000235:genetics / Q000473:pathology*; D008533:Megakaryocytes / Q000473:pathology / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009000:Monocytes / Q000473:pathology / Q000502:physiology; D022423:Myeloid Cells / Q000473:pathology* / Q000502:physiology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D013539:Simian virus 40; D019076:Transgenes
D016271:Proto-Oncogene Proteins c-myc