长链非编码RNA UCA1在小儿急性髓性白血病中的表达及其临床意义。

American journal of blood research Pub Date : 2023-01-01
Christine Wilson, Diwakar Sharma, Priyanka Swaroop, Sachin Kumar, Sameer Bakhshi, Surender K Sharawat
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引用次数: 0

摘要

长链非编码RNA (lncRNA)尿路上皮癌相关1 (UCA1)在急性髓性白血病(AML)中的潜在机制和临床意义在很大程度上是未知的。我们旨在研究lncRNA UCA1的表达及其在AML中的生物学和临床意义。lncRNA UCA1在新生AML患儿(n=69)、诱导后、完全缓解后(n=8)和复发患者(n=10)的外周血(PB)样本中表达量进行了量化。此外,还分析了两个外部队列,即TCGA-LAML数据集和白血病- mile研究。我们还量化了四种不同AML细胞系的表达,并分析了细胞分化后的表达。在我们的69例患者队列中,在基线时(P < 0.0001)以及在TCGA和Leukemia-MILE数据集中观察到AML中一致的低UCA1表达模式。在获得缓解的患者中,表达与健康个体相当,而有趣的是,复发患者的UCA1水平较低(P=0.0002)。此外,lncRNA UCA1在AML细胞系中的表达显著降低(THP-1, P=0.0112;公斤,P = 0.0168;HL-60, P=0.0112), THP-1细胞分化后升高(P=0.0001)。在我们的AML患者队列中,低表达与CR显著相关(P=0.043),然而,对生存(EFS和OS)的影响并不显著。这是首次在各种AML细胞系以及基线、缓解和复发的AML患者中研究lncRNA UCA1表达的研究。总之,我们发现与健康个体和成熟分化细胞相比,AML中的UCA1显著下调。
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Expression of long non-coding RNA UCA1 and its clinical relevance in paediatric acute myeloid leukemia.

The underlying mechanisms and clinical significance of long non-coding RNA (lncRNA) urothelial cancer associated 1 (UCA1) is largely unknown in acute myeloid leukemia (AML). We aimed to study the expression of lncRNA UCA1, and its biological and clinical relevance in AML. Expression of lncRNA UCA1 was quantified in peripheral blood (PB) samples of children with de novo AML (n=69), post-induction, after achieving complete remission (CR) (n=8), and in patients who had relapsed (n=10). Additionally, two external cohorts were analysed i.e., TCGA-LAML dataset and Leukemia-MILE study. We also quantified expression in four different AML cell lines and analysed expression after cell differentiation. A consistent pattern of low UCA1 expression in AML was observed in our cohort of sixty-nine patients at baseline (P < 0.0001) and in the TCGA and Leukemia-MILE datasets. In patients who achieved remission, expression was comparable to healthy individuals, while relapsed patients interestingly had lower levels of UCA1 (P=0.0002). Furthermore, lncRNA UCA1 expression was significantly lower in AML cell lines (THP-1, P=0.0112; KG-1, P=0.0168; and HL-60, P=0.0112) and increased when THP-1 cells were differentiated (P=0.0001). In our AML patient cohort, lower expression was significantly associated with CR (P=0.043), however, the impact on survival (EFS and OS) was not significant. This is the first study wherein the lncRNA UCA1 expression was studied in various AML cell lines along with AML patients at baseline, remission and relapse. In conclusion, we found that UCA1 is significantly downregulated in AML compared to healthy individuals and mature differentiated cells.

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来源期刊
American journal of blood research
American journal of blood research MEDICINE, RESEARCH & EXPERIMENTAL-
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