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无论细胞遗传学分组或临床结果如何,NEAT1长异构体在慢性淋巴细胞白血病中均高表达。

NEAT1 Long Isoform Is Highly Expressed in Chronic Lymphocytic Leukemia Irrespectively of Cytogenetic Groups or Clinical Outcome.

作者信息

Ronchetti Domenica, Favasuli Vanessa, Monti Paola, Cutrona Giovanna, Fabris Sonia, Silvestris Ilaria, Agnelli Luca, Colombo Monica, Menichini Paola, Matis Serena, Gentile Massimo, Nurtdinov Ramil, Guigó Roderic, Baldini Luca, Fronza Gilberto, Ferrarini Manlio, Morabito Fortunato, Neri Antonino, Taiana Elisa

机构信息

Department of Oncology and Hemato-oncology, University of Milan, 20122 Milan, Italy.

Hematology, Fondazione Cà Granda IRCCS Policlinico, 20122 Milan, Italy.

出版信息

Noncoding RNA. 2020 Mar 13;6(1):11. doi: 10.3390/ncrna6010011.

Abstract

The biological role and therapeutic potential of long non-coding RNAs (lncRNAs) in chronic lymphocytic leukemia (CLL) are still open questions. Herein, we investigated the significance of the lncRNA NEAT1 in CLL. We examined NEAT1 expression in 310 newly diagnosed Binet A patients, in normal CD19+ B-cells, and other types of B-cell malignancies. Although global NEAT1 expression level was not statistically different in CLL cells compared to normal B cells, the median ratio of NEAT1_2 long isoform and global NEAT1 expression in CLL samples was significantly higher than in other groups. NEAT1_2 was more expressed in patients carrying mutated genes. Concerning cytogenetic aberrations, NEAT1_2 expression in CLL with trisomy 12 was lower with respect to patients without alterations. Although global NEAT1 expression appeared not to be associated with clinical outcome, patients with the lowest NEAT1_2 expression displayed the shortest time to first treatment; however, a multivariate regression analysis showed that the NEAT1_2 risk model was not independent from other known prognostic factors, particularly the IGHV mutational status. Overall, our data prompt future studies to investigate whether the increased amount of the long NEAT1_2 isoform detected in CLL cells may have a specific role in the pathology of the disease.

摘要

长链非编码RNA(lncRNA)在慢性淋巴细胞白血病(CLL)中的生物学作用和治疗潜力仍是悬而未决的问题。在此,我们研究了lncRNA NEAT1在CLL中的意义。我们检测了310例新诊断的Binet A期患者、正常CD19 + B细胞以及其他类型B细胞恶性肿瘤中NEAT1的表达。虽然与正常B细胞相比,CLL细胞中NEAT1的整体表达水平在统计学上没有差异,但CLL样本中NEAT1_2长异构体与NEAT1整体表达的中位数比值显著高于其他组。NEAT1_2在携带突变基因的患者中表达更高。关于细胞遗传学异常,12号染色体三体的CLL患者中NEAT1_2的表达低于无改变的患者。虽然NEAT1的整体表达似乎与临床结局无关,但NEAT1_2表达最低的患者首次治疗时间最短;然而,多变量回归分析表明,NEAT1_2风险模型并非独立于其他已知的预后因素,尤其是IGHV突变状态。总体而言,我们的数据促使未来的研究去探究在CLL细胞中检测到的长链NEAT1_2异构体数量增加是否可能在该疾病的病理过程中具有特定作用。

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