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The role of AP-1 and epigenetics in ALCL
Ana-Iris Schiefer1,Paul Vesely4,5,Melanie R. Hassler1,Gerda Egger1,6,Lukas Kenner1,2,3,6,*
1
Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria
2
Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria
3
Unit of Pathology of Laboratory Animals (UPLA), University of Veterinary Medicine Vienna, 1210 Vienna, Austria
4
Institute of Pathology, Medical University of Graz, Graz, Austria
5
Institute of Molecular Biosciences, University of Graz, Graz, Austria
6
European Research Initiative on ALK-related malignancies (ERIA) (http://www.erialcl.net/)
DOI: 10.2741/S436 Volume 7 Issue 2, pp.226-235
Published: 01 June 2015
(This article belongs to the Special Issue ALK: 20 years of discoveries)
*Corresponding Author(s):  
Lukas Kenner
E-mail:  
lukas.kenner@meduniwien.ac.at
Abstract

Anaplastic large cell lymphoma (ALCL) is an aggressive, highly proliferative, T-cell lymphoma with increasing incidence worldwide. Anaplastic Lymphoma Kinase (ALK) fusions occur in about 50% of all cases. Most ALK positive cases of ALCL harbor the t(2;5) translocation that leads to expression of Nucleophosmin-Anaplastic Lymphoma Kinase (NPM-ALK). NPM-ALK induces a variety of oncogenic signaling pathways that lead to malignant transformation of T-cells via Activator Protein-1 (AP-1), STAT3 and other (transcription) factors. In addition to the commonly known AP-1 activators Mitogen-Activated Protein Kinases (MAPKs), there are other signaling pathways, such as PI3K/mTOR/AKT, which are implicated in AP-1 activation/expression in ALCL. The AP-1 factor JUNB was shown to drive ALCL proliferation and the expression of the characteristic ALCL Ki-1 antigen, CD30. cJUN and JUNB target PDGFRB, thereby leading to tumor progression and dissemination. Furthermore, aberrant gene expression in ALCL is frequently accompanied by changes in epigenetic regulatory mechanisms, such as DNA methylation patterns. Here, we discuss the role of AP-1 in the pathogenesis of ALCL and provide an overview of pathological epigenetic changes in ALCL cells.

Key words

ALK+ ALCL, AP-1, cJUN, JunB, CD30, NF-κB pathway, PDGFRB, Epigenetics, Review

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Ana-Iris Schiefer, Paul Vesely, Melanie R. Hassler, Gerda Egger, Lukas Kenner. The role of AP-1 and epigenetics in ALCL. Frontiers in Bioscience-Scholar. 2015. 7(2); 226-235.