Tumor suppressor TNFAIP3 (A20) is frequently deleted in Sézary syndrome

F C M Braun; P Grabarczyk; M Möbs; F K Braun; J Eberle; M Beyer; W Sterry; F Busse; J Schröder; M Delin; G K Przybylski; C A Schmidt

doi:10.1038/leu.2011.101

Tumor suppressor TNFAIP3 (A20) is frequently deleted in Sézary syndrome

Leukemia. 2011 Sep;25(9):1494-501. doi: 10.1038/leu.2011.101. Epub 2011 May 31.

Authors

F C M Braun¹, P Grabarczyk, M Möbs, F K Braun, J Eberle, M Beyer, W Sterry, F Busse, J Schröder, M Delin, G K Przybylski, C A Schmidt

Affiliation

¹ Clinic for Internal Medicine C, University Greifswald, Greifswald, Germany.

PMID: 21625233
DOI: 10.1038/leu.2011.101

Abstract

Despite recent therapeutic improvements, the prognosis for patients suffering from Sézary syndrome (SS), a disseminated form of cutaneous T-cell lymphomas, is still poor. We identified bi- and monoallelic deletions of the tumor necrosis factor-α-induced protein 3 gene (TNFAIP3; A20) in a high proportion of SS patients as well as biallelic A20 deletion in the SS-derived cell line SeAx. Furthermore, we demonstrate that inhibition of A20 activates the NF-κB pathway thereby increasing the proliferation of normal T lymphocytes. On the other hand, the reconstitution of A20 expression slowed down the cell cycle in SeAx cells. Recently A20 inactivation has been reported in various B-cell lymphomas. In this study, we show that A20 is also a putative tumor suppressor in the T-cell malignancy-SS.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Blotting, Western
Cell Cycle
Comparative Genomic Hybridization
DNA Methylation
DNA-Binding Proteins
Female
Gene Deletion*
Genes, Tumor Suppressor*
Humans
Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
Intracellular Signaling Peptides and Proteins / genetics*
Intracellular Signaling Peptides and Proteins / metabolism
Lymphocyte Activation
Male
Middle Aged
NF-kappa B / genetics
NF-kappa B / metabolism
Nuclear Proteins / antagonists & inhibitors
Nuclear Proteins / genetics*
Nuclear Proteins / metabolism
RNA, Messenger / genetics
RNA, Small Interfering / genetics
Reverse Transcriptase Polymerase Chain Reaction
Sezary Syndrome / genetics*
Sezary Syndrome / metabolism
Sezary Syndrome / pathology
Skin Neoplasms / genetics*
Skin Neoplasms / metabolism
Skin Neoplasms / pathology
T-Lymphocytes / metabolism
Tumor Cells, Cultured
Tumor Necrosis Factor alpha-Induced Protein 3

Substances

DNA-Binding Proteins
Intracellular Signaling Peptides and Proteins
NF-kappa B
Nuclear Proteins
RNA, Messenger
RNA, Small Interfering
TNFAIP3 protein, human
Tumor Necrosis Factor alpha-Induced Protein 3