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

• Published in: Leukemia Vol. 25; no. 9; pp. 1494 - 1501
• Main Authors: BRAUN, F. C. M, GRABARCZYK, P, PRZYBYLSKI, G. K, SCHMIDT, C. A, MÖBS, M, BRAUN, F. K, EBERLE, J, BEYER, M, STERRY, W, BUSSE, F, SCHRÖDER, J, DELIN, M
• Format: Journal Article
• Language: English
• Published: Avenel, NJ Nature Publishing Group 01.09.2011
• Subjects: A20 protein; Aged; Aged, 80 and over; Apoptosis; B-cell lymphoma; Biological and medical sciences; Blood; Blotting, Western; Cell Cycle; Cell death; Clonal deletion; Comparative Genomic Hybridization; DNA Methylation; DNA-Binding Proteins; Female; Gene Deletion; Genes, Tumor Suppressor; Genetic aspects; Health aspects; Hematologic and hematopoietic diseases; Humans; Hybridization; Inactivation; Internal medicine; Intracellular Signaling Peptides and Proteins - antagonists & inhibitors; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Kinases; Leukemia; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphocyte Activation; Lymphocytes; Lymphocytes B; Lymphocytes T; Lymphoma; Male; Malignancy; Medical sciences; Middle Aged; Mutation; NF-kappa B - genetics; NF-kappa B - metabolism; NF-κB protein; Nuclear Proteins - antagonists & inhibitors; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Patients; Physiological aspects; Proteins; Reverse Transcriptase Polymerase Chain Reaction; Risk factors; RNA, Messenger - genetics; RNA, Small Interfering - genetics; Sezary syndrome; Sezary Syndrome - genetics; Sezary Syndrome - metabolism; Sezary Syndrome - pathology; Skin Neoplasms - genetics; Skin Neoplasms - metabolism; Skin Neoplasms - pathology; T cells; T-Lymphocytes - metabolism; Tumor Cells, Cultured; Tumor necrosis factor; Tumor Necrosis Factor alpha-Induced Protein 3; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Tumor suppressor genes; Poland; Germany; United States > US; Berlin Germany; Cutaneous T cell lymphoma; Skin disease; Hematology; TNFAIP3; Malignant hemopathy; Lymphoid neoplasm; Non Hodgkin lymphoma; Gene expression; FT-CGH; Peripheral T cell lymphoma; Chronic; Cutaneous hematologic disease; Comparative genomic hybridization; Sezary syndrome; Cell death; Lymphoproliferative syndrome; Cell cycle; Deletion; Cancer; Apoptosis; Tumor suppressor gene; A20
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/leu.2011.101

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.