IMR Press / FBS / Volume 7 / Issue 2 / DOI: 10.2741/S436

Frontiers in Bioscience-Scholar (FBS) is published by IMR Press from Volume 13 Issue 1 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

The role of AP-1 and epigenetics in ALCL
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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) (

*Author to whom correspondence should be addressed.

Academic Editor: Roberto Chiarle

Front. Biosci. (Schol Ed) 2015, 7(2), 226–235;
Published: 1 June 2015
(This article belongs to the Special Issue ALK: 20 years of discoveries)

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.

NF-κB pathway
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