Oncotarget

Research Papers:

Ectopic expression of transcription factor BATF3 induces B-cell lymphomas in a murine B-cell transplantation model

Christian Weiser, Mina V. Petkova, Benjamin Rengstl, Claudia Döring, Dorothee von Laer, Sylvia Hartmann, Ralf Küppers _, Martin-Leo Hansmann and Sebastian Newrzela

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Oncotarget. 2018; 9:15942-15951. https://doi.org/10.18632/oncotarget.24639

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Abstract

Christian Weiser1, Mina V. Petkova2, Benjamin Rengstl1, Claudia Döring1, Dorothee von Laer3, Sylvia Hartmann1, Ralf Küppers4,5, Martin-Leo Hansmann1,5,* and Sebastian Newrzela1,*

1Dr. Senckenberg Institute of Pathology, Goethe-University of Frankfurt, Medical School, Frankfurt am Main, Germany

2Experimental and Clinical Research Center (ECRC), Medical Faculty of the Charité and Max Delbrück Center for Molecular Medicine, Berlin, Germany

3Division of Virology, Department of Hygiene, Microbiology, Social Medicine Medical University IBK, Innsbruck, Austria

4Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Medical School, Essen, Germany

5German Cancer Consortium (DKTK), Heidelberg, Germany

*Shared senior authors

Correspondence to:

Ralf Küppers, email: ralf.kueppers@uk-essen.de

Keywords: BATF3; B-cell immunology; B-cell lymphoma; germinal center; oncogene

Received: March 13, 2017    Accepted: February 24, 2018    Published: March 23, 2018

ABSTRACT

The mechanisms involved in malignant transformation of mature B and T lymphocytes are still poorly understood. In a previous study, we compared gene expression profiles of the tumor cells of Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) to their normal cellular counterparts and found the basic leucine zipper protein ATF-like 3 (BATF3) to be significantly upregulated in the tumor cells of both entities. To assess the oncogenic potential of BATF3 in lymphomagenesis and to dissect the molecular interactions of BATF3 in lymphoma cells, we retrovirally transduced murine mature T and B cells with a BATF3-encoding viral vector and transplanted each population into Rag1-deficient recipients. Intriguingly, BATF3-expressing B lymphocytes readily induced B-cell lymphomas after characteristic latencies, whereas T-cell transplanted animals remained healthy throughout the observation time. Further analyses revealed a germinal center B-cell-like phenotype of most BATF3-initiated lymphomas. In a multiple myeloma cell line, BATF3 inhibited BLIMP1 expression, potentially illuminating an oncogenic action of BATF3 in B-cell lymphomagenesis. In conclusion, BATF3 overexpression induces malignant transformation of mature B cells and might serve as a potential target in B-cell lymphoma treatment.


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