A new model of LMP1-MYC interaction in B cell lymphoma

Evelena P Ontiveros; Ahmad Halwani; Laura L Stunz; Natalie Kamberos; Alicia K Olivier; Siegfried Janz; Gail A Bishop

doi:10.3109/10428194.2014.900762

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A new model of LMP1-MYC interaction in B cell lymphoma

Journal article

Peer reviewed

A new model of LMP1-MYC interaction in B cell lymphoma

Evelena P Ontiveros, Ahmad Halwani, Laura L Stunz, Natalie Kamberos, Alicia K Olivier, Siegfried Janz and Gail A Bishop

Leukemia & lymphoma, Vol.55(12), pp.2917-2923

12/01/2014

DOI: 10.3109/10428194.2014.900762

PMCID: PMC4207734

PMID: 24605938

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Abstract

Epstein-Barr virus (EBV) is associated with aggressive B cell lymphomas (BCLs). Latent membrane protein 1 (LMP1) of EBV is an oncogenic protein required for EBV B cell transformation. However, LMP1 is a weak oncogene in mice. Mice expressing Myc inserted 5' of the Eμ enhancer (iMyc Eμ ), mimicking the t(8;14) translocation of endemic Burkitt lymphoma, develop delayed onset BCLs. To investigate potential cooperation between LMP1 and oncogenic MYC, we produced mice expressing the LMP1 signaling domain via a hybrid CD40-LMP1 transgene (mCD40-LMP1), and the dysregulated MYC protein of aggressive EBV+ BCLs. mCD40-LMP1/iMyc Eμ mice trended toward earlier BCL onset. BCLs from mCD40-LMP1/iMyc Eμ mice expressed LMP1 and were transplantable into immunocompetent recipients. iMyc Eμ and mCD40-LMP1/iMyc Eμ mice developed BCLs with similar immunophenotypes. LMP1 signaling was intact in BCLs as shown by inducible interleukin-6. Additionally, LMP1 signaling to tumor cells induced the two isoforms of Pim1, a constitutively active prosurvival kinase implicated in lymphomagenesis.

LMP1

MYC

lymphoma

Details

Title: Subtitle: A new model of LMP1-MYC interaction in B cell lymphoma
Creators: Evelena P Ontiveros - Division of Hematology and Oncology, Department of Internal Medicine
Ahmad Halwani - Division of Hematology and Oncology, Department of Internal Medicine
Laura L Stunz - Department of Microbiology
Natalie Kamberos - Division of Hematology and Oncology, Department of Pediatrics
Alicia K Olivier - Department of Pathology
Siegfried Janz - Holden Comprehensive Cancer Center, The University of Iowa Roy J. and Lucille A. Carver College of Medicine
Gail A Bishop - University of Iowa
Resource Type: Journal article
Publication Details: Leukemia & lymphoma, Vol.55(12), pp.2917-2923
DOI: 10.3109/10428194.2014.900762
PMID: 24605938
PMCID: PMC4207734
NLM abbreviation: Leuk Lymphoma
ISSN: 1042-8194
eISSN: 1029-2403
Publisher: Informa UK Limited
Language: English
Date published: 12/01/2014
Academic Unit: Microbiology and Immunology; President; Pathology
Record Identifier: 9984001136302771

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