Zhang Ting-Juan, Lin Jiang, Zhou Jing-Dong, Li Xi-Xi, Zhang Wei, Guo Hong, Xu Zi-Jun, Yan Yang, Ma Ji-Chun, Qian Jun
Department of Hematology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China; The Key Lab of Precision Diagnosis and Treatment of Zhenjiang City, Zhenjiang, Jiangsu, People's Republic of China; School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
Laboratory Center, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China; The Key Lab of Precision Diagnosis and Treatment of Zhenjiang City, Zhenjiang, Jiangsu, People's Republic of China; School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
Gene. 2018 Jan 15;640:79-85. doi: 10.1016/j.gene.2017.10.034. Epub 2017 Oct 12.
Oncogenic role of miR-19 family has been identified in human cancers especially in lymphoid malignancies. However, to date, little studies investigated the role of miR-19 family in myeloid malignancies. Herein, we examined miR-19a/b expression and explored its clinical significance in de novo acute myeloid leukemia (AML). The detection of miR-19a/b expression was performed by real-time quantitative PCR in bone marrow mononuclear cells of 113 patients and 42 healthy donors. Both miR-19a/b levels were significantly increased in AML patients in contrast to controls. Patients with miR-19a/b overexpression were more frequently occurred in female, and had an older age. Moreover, cases with miR-19a overexpression had a higher frequency of U2AF1, C-KIT and CEBPA mutations, whereas miR-19b overexpressed cases harbored U2AF1 and IDH1/2 mutations. There was no significant association of miR-19a overexpression with complete remission (CR) rate and overall survival (OS) among whole-cohort AML, non-M3 AML, and cytogenetically normal AML (CN-AML). However, although miR-19b overexpression was not correlated with CR rate, patients with miR-19b overexpression presented significantly shorter OS in whole-cohort AML and a trend in non-M3 AML and CN-AML patients. Importantly, our data also showed that miR-19a/b expression level at CR phase was lower than diagnosis time, and was returned to primary level even higher when at relapse phase. Our findings revealed that miR-19a/b overexpression were frequent events in de novo AML patients. Moreover, up-regulation of miR-19b expression was associated with poor prognosis and disease recurrence in AML.
miR-19家族的致癌作用已在人类癌症中得到证实，尤其是在淋巴系统恶性肿瘤中。然而，迄今为止，很少有研究探讨miR-19家族在髓系恶性肿瘤中的作用。在此，我们检测了miR-19a/b的表达，并探讨了其在初发急性髓系白血病（AML）中的临床意义。采用实时定量PCR检测了113例患者和42例健康供者骨髓单个核细胞中miR-19a/b的表达。与对照组相比，AML患者中miR-19a/b水平均显著升高。miR-19a/b过表达的患者女性更为常见，且年龄较大。此外，miR-19a过表达的病例中U2AF1、C-KIT和CEBPA突变的频率较高，而miR-19b过表达的病例则存在U2AF1和IDH1/2突变。在整个队列的AML、非M3 AML和细胞遗传学正常的AML（CN-AML）中，miR-19a过表达与完全缓解（CR）率和总生存期（OS）之间无显著相关性。然而，虽然miR-19b过表达与CR率无关，但在整个队列的AML患者中，miR-19b过表达的患者OS显著缩短，在非M3 AML和CN-AML患者中也有这种趋势。重要的是，我们的数据还显示，CR期的miR-19a/b表达水平低于诊断时，复发期时甚至恢复到更高的初始水平。我们的研究结果表明，miR-19a/b过表达在初发AML患者中很常见。此外，miR-19b表达上调与AML患者的不良预后和疾病复发相关。
