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长链非编码 RNA ANRIL 是急性髓细胞白血病疾病进展和预后不良的潜在指标。

Long non‑coding RNA ANRIL is a potential indicator of disease progression and poor prognosis in acute myeloid leukemia.

机构信息

Department of Hematology, Central Hospital of Xiangtan, Xiangtan, Hunan 411100, P.R. China.

出版信息

Mol Med Rep. 2021 Feb;23(2). doi: 10.3892/mmr.2020.11751. Epub 2020 Dec 10.

Abstract

The present study explored the association of long non‑coding RNA (lncRNA) antisense non‑coding RNA in the INK4 locus (ANRIL) with the development of acute myeloid leukemia (AML) clinical features and prognosis of patients with AML. Bone marrow mononuclear cells (BMMCs) were obtained from 178 patients with AML prior to initial therapy and from 30 healthy donors. The expression of lncRNA ANRIL in BMMCs was detected by reverse transcription‑quantitative PCR. Complete remission (CR) was assessed after induction therapy. Event‑free survival (EFS) and overall survival (OS) were evaluated during the follow‑up. The levels of lncRNA ANRIL were increased in patients with AML compared with those in healthy donors and were capable of distinguishing patients with AML from healthy donors (area under the curve, 0.886; 95% CI, 0.820‑0.952). Furthermore, lncRNA ANRIL was associated with an increased occurrence internal tandem duplications in the FMS‑like tyrosine kinase 3, decreased occurrence inv(16) or t(16;6), intermediate‑risk and poor‑risk stratification while no association of lncRNA ANRIL was identified with French‑American‑British classification, cytogenetics, isolated biallelic CCAAT/enhancer‑binding protein α mutation and nucleophosmin 1 mutation in patients with AML. Furthermore, lncRNA ANRIL was significantly associated with a lower CR rate. In addition, EFS and OS were shorter in patients with high expression of lncRNA ANRIL compared with those in patients with low expression of lncRNA ANRIL. Multivariate Cox regression analyses revealed that high expression of lncRNA ANRIL, poor‑risk stratification and white blood cells (>10.0x10 cells/l) were independent prognostic factors for shorter EFS, while high expression of lncRNA ANRIL and poorer risk stratification were independent prognostic factors for shorter OS. The present results suggested that lncRNA ANRIL has clinical relevance as a biomarker for assisting diagnosis treatment decisions and prognosis prediction and the identification of potential drug target for AML.

摘要

本研究探讨了长非编码 RNA(lncRNA)反义非编码 RNA 在 INK4 基因座(ANRIL)与急性髓系白血病(AML)患者临床特征和预后的关系。在初始治疗前,从 178 例 AML 患者和 30 例健康供者中获得骨髓单个核细胞(BMMC)。采用逆转录-定量 PCR 检测 BMMC 中 lncRNA ANRIL 的表达。在诱导治疗后评估完全缓解(CR)。在随访期间评估无事件生存(EFS)和总生存(OS)。与健康供者相比,AML 患者的 lncRNA ANRIL 水平升高,能够将 AML 患者与健康供者区分开来(曲线下面积,0.886;95%CI,0.820-0.952)。此外,lncRNA ANRIL 与 FMS 样酪氨酸激酶 3 内串联重复的发生率增加、inv(16)或 t(16;6)的发生率降低、中危和不良风险分层有关,而与 AML 患者的 French-American-British 分类、细胞遗传学、孤立双等位 CCAAT/增强子结合蛋白α突变和核磷蛋白 1 突变无关。此外,lncRNA ANRIL 与较低的 CR 率显著相关。此外,与 lncRNA ANRIL 低表达的患者相比,lncRNA ANRIL 高表达的患者的 EFS 和 OS 更短。多变量 Cox 回归分析显示,lncRNA ANRIL 高表达、不良风险分层和白细胞(>10.0x10 细胞/l)是 EFS 较短的独立预后因素,而 lncRNA ANRIL 高表达和较差的风险分层是 OS 较短的独立预后因素。本研究结果表明,lncRNA ANRIL 作为一种辅助诊断、治疗决策和预后预测的生物标志物具有临床相关性,并为 AML 潜在的药物靶点提供了依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d331/7723160/58c3214ac5ad/mmr-23-02-11751-g00.jpg

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