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Free keywords:
Base Sequence; Basic Helix-Loop-Helix Transcription Factors/*deficiency/genetics; Cell Cycle/genetics; Cell Line; Cell Proliferation; Comparative Genomic Hybridization; Cyclin-Dependent Kinase 6/metabolism; DNA Primers/genetics; Electrophoretic Mobility Shift Assay; Flow Cytometry; *Gene Deletion; Gene Expression Profiling; Gene Expression Regulation, Neoplastic/*genetics; Genes, T-Cell Receptor beta/genetics; Genome, Human/*genetics; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Leukocytes, Mononuclear; Molecular Sequence Data; Proto-Oncogene Proteins c-myc/metabolism; Reverse Transcriptase Polymerase Chain Reaction; Sequence Analysis, DNA; Sezary Syndrome/*genetics; Signal Transduction/*genetics; ras Proteins/metabolism
Abstract:
The transcription factor E2A is essential for lymphocyte development. In this study, we describe a recurrent E2A gene deletion in at least 70% of patients with Sezary syndrome (SS), a subtype of T cell lymphoma. Loss of E2A results in enhanced proliferation and cell cycle progression via derepression of the protooncogene MYC and the cell cycle regulator CDK6. Furthermore, by examining the gene expression profile of SS cells after restoration of E2A expression, we identify several E2A-regulated genes that interfere with oncogenic signaling pathways, including the Ras pathway. Several of these genes are down-regulated or lost in primary SS tumor cells. These data demonstrate a tumor suppressor function of E2A in human lymphoid cells and could help to develop new treatment strategies for human lymphomas with altered E2A activity.
