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Inactivation of RUNX3/p46 Promotes Cutaneous T-Cell Lymphoma.
Haider, Ahmed; Steininger, Anne; Ullmann, Reinhard; Hummel, Michael; Dimitrova, Lora; Beyer, Marc; Vandersee, Staffan; Lenze, Dido; Sterry, Wolfram; Assaf, Chalid; Möbs, Markus.
Afiliação
  • Haider A; Department of Dermatology, Charité - Universitaetsmedizin Berlin, Berlin, Germany.
  • Steininger A; Max Planck Institute for Molecular Genetics, Berlin, Germany.
  • Ullmann R; Max Planck Institute for Molecular Genetics, Berlin, Germany; Institut für Radiobiologie der Bundeswehr in Verbindung mit der Universität Ulm, Munich, Germany.
  • Hummel M; Institute of Pathology, Charité - Universitaetsmedizin Berlin, Berlin, Germany.
  • Dimitrova L; Institute of Pathology, Charité - Universitaetsmedizin Berlin, Berlin, Germany.
  • Beyer M; Department of Dermatology, Charité - Universitaetsmedizin Berlin, Berlin, Germany.
  • Vandersee S; Department of Dermatology, Charité - Universitaetsmedizin Berlin, Berlin, Germany; Central German Armed Forces hospital, Department of Dermatology and Allergy, Koblenz, Germany.
  • Lenze D; Institute of Pathology, Charité - Universitaetsmedizin Berlin, Berlin, Germany.
  • Sterry W; Department of Dermatology, Charité - Universitaetsmedizin Berlin, Berlin, Germany.
  • Assaf C; Department of Dermatology, Charité - Universitaetsmedizin Berlin, Berlin, Germany; Department of Dermatology, HELIOS Klinikum Krefeld, Krefeld, Germany. Electronic address: chalid.assaf@charite.de.
  • Möbs M; Department of Dermatology, Charité - Universitaetsmedizin Berlin, Berlin, Germany; Institute of Pathology, Charité - Universitaetsmedizin Berlin, Berlin, Germany. Electronic address: markus.moebs@charite.de.
J Invest Dermatol ; 136(11): 2287-2296, 2016 11.
Article em En | MEDLINE | ID: mdl-27377697
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/p46low cell 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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: RNA Mensageiro / Regulação Neoplásica da Expressão Gênica / Linfoma Cutâneo de Células T / Subunidade alfa 3 de Fator de Ligação ao Core Idioma: En Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: RNA Mensageiro / Regulação Neoplásica da Expressão Gênica / Linfoma Cutâneo de Células T / Subunidade alfa 3 de Fator de Ligação ao Core Idioma: En Ano de publicação: 2016 Tipo de documento: Article