Deregulation of ETS1 and FLI1 contributes to the pathogenesis of diffuse large B-cell lymphoma

ETS1 和 FLI1 失调导致弥漫性大 B 细胞淋巴瘤的发病

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作者:Paola Bonetti, Monica Testoni, Marta Scandurra, Maurilio Ponzoni, Roberto Piva, Afua A Mensah, Andrea Rinaldi, Ivo Kwee, Maria Grazia Tibiletti, Javeed Iqbal, Timothy C Greiner, Wing-Chung Chan, Gianluca Gaidano, Miguel A Piris, Franco Cavalli, Emanuele Zucca, Giorgio Inghirami, Francesco Bertoni

Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common form of human lymphoma. DLBCL is a heterogeneous disease characterized by different genetic lesions. We herein report the functional characterization of a recurrent gain mapping on chromosome 11q24.3, found in 23% of 166 DLBCL cases analyzed. The transcription factors ETS1 and FLI1, located within the 11q24.3 region, had significantly higher expression in clinical samples carrying the gain. Functional studies on cell lines showed that ETS1 and FLI1 cooperate in sustaining DLBCL proliferation and viability and regulate genes involved in germinal center differentiation. Taken together, these data identify the 11q24.3 gain as a recurrent lesion in DLBCL leading to ETS1 and FLI1 deregulated expression, which can contribute to the pathogenesis of this disease.

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