title: The role of AP-1 and epigenetics in ALCL.
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.
authors.forename: Ana-Iris
authors.initials: AI
authors.lastname: Schiefer
authors.forename: Paul
authors.initials: P
authors.lastname: Vesely
authors.forename: Melanie R
authors.initials: MR
authors.lastname: Hassler
authors.forename: Gerda
authors.initials: G
authors.lastname: Egger
authors.affiliation: Clinical Institute of Pathology, Medical University of Vienna, Wahringer Gürtel 18-20, A-1090 Vienna, Austria, lukas.kenner@meduniwien.ac.at.
authors.forename: Lukas
authors.initials: L
authors.lastname: Kenner
mesh_terms: D000818:Animals; D044127:Epigenesis, Genetic; D006801:Humans; D017728:Lymphoma, Large-Cell, Anaplastic / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D018808:Transcription Factor AP-1