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ETS1 和 FLI1 的失调导致弥漫性大 B 细胞淋巴瘤的发病机制。

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

机构信息

Lymphoma and Genomics Research Program, Institute of Oncology Research, Bellinzona, Switzerland;

出版信息

Blood. 2013 Sep 26;122(13):2233-41. doi: 10.1182/blood-2013-01-475772. Epub 2013 Aug 7.

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.

摘要

弥漫性大 B 细胞淋巴瘤(DLBCL)是最常见的人类淋巴瘤形式。DLBCL 是一种异质性疾病,其特征是存在不同的遗传病变。我们在此报告了在分析的 166 例 DLBCL 病例中,有 23%存在 11q24.3 染色体上反复出现的增益映射的功能特征。位于 11q24.3 区域内的转录因子 ETS1 和 FLI1,在携带增益的临床样本中表达显著升高。细胞系的功能研究表明,ETS1 和 FLI1 合作维持 DLBCL 的增殖和活力,并调节与生发中心分化相关的基因。总之,这些数据表明 11q24.3 增益是 DLBCL 中的一种复发性病变,导致 ETS1 和 FLI1 表达失控,这可能有助于该疾病的发病机制。

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