Gene expression profiling of the Se-Ax cell line following E2A reconstitution. Homo sapiens

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 Sézary syndrome (SS), a subtype of T cell lymphoma. Loss of E2A results in enhanced proliferation and cell cycle progression via derepression of the proto-oncogene MYC and the cell cycle regulator CDK6. Furthermore, by examining the gene expression profile of SS cells following restoration of E2A expression, we identify a number of 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. Overall design: The E2A-deficient Sézary cell line Seax was transiently transfected with the E2A-expression constructs E47myc (a myc-tagged E47 construct) or E47-forced dimer (a construct coding for two covalently linked E47 molecules), respectively. Every experiment was performed as two replicates accompanied by control transfections with a Mock plasmid.