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首页> 外文期刊>Journal of Cellular Physiology >Hypomethylation‐mediated H19 H19 overexpression increases the risk of disease evolution through the association with BCR‐ABL BCR‐ABL transcript in chronic myeloid leukemia
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Hypomethylation‐mediated H19 H19 overexpression increases the risk of disease evolution through the association with BCR‐ABL BCR‐ABL transcript in chronic myeloid leukemia

机译：Hypomethylation介导段H19段H19超表达会增加疾病的风险通过进化该协会与BCR ABL BCR ABL应承担的成绩单在慢性粒细胞白血病

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摘要

Previous study has revealed that H19 expression is required for efficient tumor growth induced by BCR‐ABL in chronic myeloid leukemia (CML). Herein, we further determined H19 expression and its clinical implication in patients with CML. H19 expression and methylation were detected by real‐time quantitative PCR and real‐time quantitative methylation‐specific PCR, and then clinical implication of H19 expression was further analyzed. H19 expression was significantly up‐regulated in CML patients ( p? ?0.001). H19 expression with an area under receiver operating characteristic curve value of 0.824 might serve as a promising biomarker in distinguishing CML patients from controls. The patients with high H19 expression had a tendency of higher white blood cells and BCR‐ABL transcript than those with low H19 expression. H19 overexpression occurred with the higher frequency in blast crisis stage (11/11, 100%), lower in accelerated phase (3/5, 60%), and chronic phase (42/62, 66%) stages. Moreover, paired patients during disease progression with increased BCR‐ABL transcript also showed a significant upregulation of H19 expression. Meanwhile, H19 expression was decreased in follow‐up patients who achieved complete molecular remission after tyrosine kinase inhibitors‐based therapy. Epigenetic studies showed that H19 differentially methylated region/imprinting control region (DMR/ICR) was hypomethylated and associated with H19 expression in CML patients. Moreover, demethylation of H19 DMR/ICR reactivated H19 expression in K562 cells. Collectively, H19 overexpression, a frequent event in CML, was associated with higher BCR‐ABL transcript involving in disease progression. Moreover, H19 DMR/ICR hypomethylation in CML may be one of the mechanisms mediating H19 overexpression.
机译：先前的研究已经表明段H19表达式需要有效的引起的肿瘤生长BCR ABL应承担在慢性粒细胞白血病(CML)。在此,我们进一步段H19表达和决定在CML患者的临床意义。段H19表达式和甲基化被检测到实时定量PCR和实时定量的甲基化检测特定PCR,然后段H19表达的临床意义进一步分析。明显应承担监管在CML患者(p ?& ? 0.001)。接受者操作特性曲线的值0.824可能作为一种很有前途的生物标志物区分CML患者和控制。患者高段H19表达式有一个趋势更高的白细胞和BCR ABL记录比低段H19表达式。段H19超表达与更高的发生频率在爆炸危机阶段(11/11,100%),低在加速阶段(3/5,60%)慢性阶段(42/62,66%)阶段。患者在疾病进展增加BCR ABL记录也显示重要的upregulation段H19表达式。与此同时,段H19表达减少遵循了应承担的患者完整的实现分子的酪氨酸激酶后缓解抑制剂的基础治疗。显示段H19差异甲基化区域/印记控制区域(DMR / ICR)与段H19 hypomethylated和相关的表达式在CML患者。DMR / ICR再生段H19 K562细胞中表达。总的来说,段H19过度频繁事件在CML与更高的BCR ABL应承担的记录包括在疾病进展。此外,段H19 DMR / ICR hypomethylation CML是中介段H19的机制之一超表达。

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