Gene knockdown studies revealed CCDC50 as a candidate gene in mantle cell lymphoma and chronic lymphocytic leukemia
Gene knockdown studies revealed CCDC50 as a candidate gene in mantle cell lymphoma and chronic lymphocytic leukemia
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DOI：
10.1038/leu.2009.144
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发表时间：
2009-11-01
期刊：
影响因子：
11.4
通讯作者：
Pscherer, A.
中科院分区：
文献类型：
--
作者：
Farfsing, A.;Engel, F.;Pscherer, A.
两种B细胞非霍奇金淋巴瘤实体，慢性淋巴细胞性白血病(CLL)和套细胞淋巴瘤(MCL)，显示出3q25-q29，12q13-q14和18q21-q22的复发性染色体增加。这些像差影响的病理机制尚不清楚。这项研究的目的是确定位于这些获得的区域内的基因，这些基因控制着MCL和CLL癌细胞的细胞死亡和细胞存活。对18例CLL和6例MCL患者以及代表这两种肿瘤的6个细胞系的血液样本进行了基因表达谱分析。通过基因组DNA和基因表达的比较，确定了72个候选基因。我们对这些候选基因进行了有限的RNA干扰筛选，以确定影响细胞存活的基因。CCDC50、SERPINI2和SMARCC2介导了原代CLL细胞和细胞系的细胞活力下降。基因敲除和核转录因子kappaB(NFkappa B)报告基因分析表明，CCDC50是MCL和CLL细胞生存所必需的，并控制着NFkappa B信号转导。白血病(2009年)23,2018年-2026年；doi：10.1038/leU.S.2009.144；在线发布2009年7月30日
The two B-cell non-Hodgkin's lymphoma entities, chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), show recurrent chromosomal gains of 3q25-q29, 12q13-q14 and 18q21-q22. The pathomechanisms affected by these aberrations are not understood. The aim of this study was to identify genes, located within these gained regions, which control cell death and cell survival of MCL and CLL cancer cells. Blood samples collected from 18 patients with CLL and 6 patients with MCL, as well as 6 cell lines representing both malignancies were analyzed by gene expression profiling. By a comparison of genomic DNA and gene expression, 72 candidate genes were identified. We performed a limited RNA interference screening with these candidates to identify genes affecting cell survival. CCDC50 (coiled coil domain containing protein 50), SERPINI2 and SMARCC2 mediated a reduction of cell viability in primary CLL cells as well as in cell lines. Gene knockdown and a nuclear factor kappa B (NF kappa B) reporter gene assay revealed that CCDC50 is required for survival in MCL and CLL cells and controls NF kappa B signaling. Leukemia (2009) 23, 2018-2026; doi:10.1038/leu.2009.144; published online 30 July 2009