Abstract
Mice transgenic for the leukemia oncogene E2A-PBX1 invariably develop lethal, high-grade T-cell lymphomas by 5 months of age. In this study, retroviral insertional mutagenesis was employed to identify oncogenes that cooperate with the E2A-PBX1 transgene in lymphomagenesis. Neonatal retroviral infection substantially reduced length of survival due to accelerated development of lymphomas (81 versus 130 days). The Pim1 gene was targeted by retroviral insertions in 48% of accelerated lymphomas whereas less than 5% contained activated c-Myc and none contained activated Pim2. However, Pim1 DNA rearrangements were frequently sub-stoichiometric and not present at all sites of involvement in an otherwise monoclonal lymphoma indicating that Pim1 activation occurred late in the course of lymphomagenesis. Tumor subpopulations containing activated Pim1 alleles displayed a substantial growth advantage over Pim1 negative cells following serial transfer to secondary, syngeneic recipients. Cooperative interactions were observed in intercrossed Pim1 and E2A-PBX1 transgenic mice in which all double transgenic progeny developed lethal, diffuse T lineage lymphomas by 3 months of age, whereas only 13% of E2A-PBX1 and none of Pim1 single transgenic intercross progeny developed lymphomas by 1 year. Tumors from double transgenic mice were monoclonal providing evidence that additional genetic events were required for transformation. Therefore, Pim1 and E2a-Pbx1 cooperate in T lineage lymphomagenesis but they are not sufficient and the role of Pim1 is more likely to be associated with tumor progression.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Feldman, B., Reid, T. & Cleary, M. Pim1 cooperates with E2a-Pbx1 to facilitate the progression of thymic lymphomas in transgenic mice. Oncogene 15, 2735–2742 (1997). https://doi.org/10.1038/sj.onc.1201670
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1201670
Keywords
This article is cited by
-
Pim kinases in hematological malignancies: where are we now and where are we going?
Journal of Hematology & Oncology (2014)
-
High-throughput insertional mutagenesis screens in mice to identify oncogenic networks
Nature Reviews Cancer (2009)
-
The role of E2A-PBX1 in leukemogenesis
Oncogene (2001)
-
EB-1, a tyrosine kinase signal transduction gene, is transcriptionally activated in the t(1;19) subset of pre-B ALL, which express oncoprotein E2a-Pbx1
Oncogene (1999)
-
Reassessing the role of C-MYB in tumorigenesis
Oncogene (1999)