title: Inactivation of RUNX3/p46 Promotes Cutaneous T-Cell Lymphoma.
abstract: The key role of RUNX3 in physiological T-cell differentiation has been extensively documented. However, information on its relevance for the development of human T-cell lymphomas or leukemias is scarce. Here, we show that alterations of RUNX3 by either heterozygous deletion or methylation of its distal promoter can be observed in the tumor cells of 15 of 21 (71%) patients suffering from Sézary syndrome, an aggressive variant of cutaneous T-cell lymphoma. As a consequence, mRNA levels of RUNX3/p46, the isoform controlled by the distal promoter, are significantly lower in Sézary syndrome tumor cells. Re-expression of RUNX3/p46 reduces cell viability and promotes apoptosis in a RUNX3/p46lowcell line of cutaneous T-cell lymphoma. Based on this, we present evidence that RUNX3 can act as a tumor suppressor in a human T-cell malignancy and suggest that this effect is predominantly mediated through transcripts from its distal promoter, in particular RUNX3/p46.
authors.affiliation: Department of Dermatology, Charité - Universitaetsmedizin Berlin, Berlin, Germany.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Haider
authors.affiliation: Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Steininger
authors.affiliation: Max Planck Institute for Molecular Genetics, Berlin, Germany; Institut für Radiobiologie der Bundeswehr in Verbindung mit der Universität Ulm, Munich, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Ullmann
authors.affiliation: Institute of Pathology, Charité - Universitaetsmedizin Berlin, Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hummel
authors.affiliation: Institute of Pathology, Charité - Universitaetsmedizin Berlin, Berlin, Germany.
authors.forename: Lora
authors.initials: L
authors.lastname: Dimitrova
authors.affiliation: Department of Dermatology, Charité - Universitaetsmedizin Berlin, Berlin, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Beyer
authors.affiliation: Department of Dermatology, Charité - Universitaetsmedizin Berlin, Berlin, Germany; Central German Armed Forces hospital, Department of Dermatology and Allergy, Koblenz, Germany.
authors.forename: Staffan
authors.initials: S
authors.lastname: Vandersee
authors.affiliation: Institute of Pathology, Charité - Universitaetsmedizin Berlin, Berlin, Germany.
authors.forename: Dido
authors.initials: D
authors.lastname: Lenze
authors.affiliation: Department of Dermatology, Charité - Universitaetsmedizin Berlin, Berlin, Germany.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Sterry
authors.affiliation: Department of Dermatology, Charité - Universitaetsmedizin Berlin, Berlin, Germany; Department of Dermatology, HELIOS Klinikum Krefeld, Krefeld, Germany. Electronic address: chalid.assaf@charite.de.
authors.forename: Chalid
authors.initials: C
authors.lastname: Assaf
authors.affiliation: Department of Dermatology, Charité - Universitaetsmedizin Berlin, Berlin, Germany; Institute of Pathology, Charité - Universitaetsmedizin Berlin, Berlin, Germany. Electronic address: markus.moebs@charite.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Möbs
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D045744:Cell Line, Tumor; D050677:Core Binding Factor Alpha 3 Subunit / Q000096:biosynthesis / Q000235:genetics*; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D016410:Lymphoma, T-Cell, Cutaneous / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics*
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; D012333:RNA, Messenger; C493729:Runx3 protein, human