Upregulation of the proto-oncogene Bmi-1 predicts a poor prognosis in pediatric acute lymphoblastic leukemia.
Upregulation of the proto-oncogene Bmi-1 predicts a poor prognosis in pediatric acute lymphoblastic leukemia.
复制标题
原癌基因BMI-1的上调预测小儿急性淋巴细胞白血病的预后不佳。
DOI：
10.1186/s12885-017-3049-3
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发表时间：
2017-01-25
期刊：
影响因子：
3.8
通讯作者：
Xu L
中科院分区：
文献类型：
--
作者：
Peng HX;Liu XD;Luo ZY;Zhang XH;Luo XQ;Chen X;Jiang H;Xu L
Bmi-1是B细胞特异性莫洛尼鼠白血病病毒插入位点1，是多梳组（PcG）家族的成员，在多种肿瘤中作为癌基因;然而，其表达与急性淋巴细胞白血病（ALL）儿科患者的预后相关尚未得到充分研究。采用qRT-PCR方法检测104例ALL患儿和18例正常对照者骨髓中Bmi-1的表达水平。分析Bmi-1表达与儿童ALL临床病理特征的关系，并采用Kaplan-Meier法计算Bmi-1与儿童ALL预后的相关性。此外，研究了Bmi-1表达与其转录调节因子Sall 4之间的关联。与正常对照组相比，原发性儿童ALL患者Bmi-1水平上调。然而，这些水平在达到完全缓解的患者中急剧下降。观察到Bmi-1水平升高与泼尼松反应不良以及临床风险增加之间存在显著正相关。在诊断时过度表达Bmi-1的患者的无复发生存率（RFS）较低（75.8%），而Bmi-1表达较低的患者的RFS为94.1%。ALL患者Bmi-1 mRNA表达与Sall 4a mRNA表达呈正相关。综上所述，这些数据表明，Bmi-1可以作为一种新的预后生物标志物在儿童原发性ALL，并可能部分调节Sall 4a。我们的研究还表明，Bmi-1可以作为一个新的治疗儿童ALL的治疗靶点。本文的在线版本（doi：10.1186/s12885-017-3049-3）包含补充材料，可供授权用户使用。
Bmi-1, the B cell-specific moloney murine leukemia virus insertion site 1, is a member of the Polycomb-group (PcG) family and acts as an oncogene in various tumors; however, its expression related to the prognosis of pediatric patients with acute lymphoblastic leukemia (ALL) has not been well studied. The Bmi-1 expression levels in the bone marrow of 104 pediatric ALL patients and 18 normal control subjects were determined by using qRT-PCR. The association between the Bmi-1 expression and the clinicopathological characteristics of pediatric ALL patients was analyzed, and the correlation between Bmi-1 and the prognosis of pediatric ALL was calculated according to the Kaplan–Meier method. Furthermore, the association between Bmi-1 expression and its transcriptional regulator Sall4 was investigated. Compared to normal control subjects, patients with primary pediatric ALL exhibited upregulated levels of Bmi-1. However, these levels were sharply decreased in patients who achieved complete remission. A significant positive association between elevated Bmi-1 levels and a poor response to prednisone as well as an increased clinical risk was observed. Patients who overexpressed Bmi-1 at the time of diagnosis had a lower relapse-free survival (RFS) rate (75.8%), whereas patients with lower Bmi-1 expression had an RFS of 94.1%. Furthermore, in ALL patients, the mRNA expression of Bmi-1 was positively correlated to the mRNA expression of Sall4a. Taken together, these data suggest that Bmi-1 could serve as a novel prognostic biomarker in pediatric primary ALL and may be partially regulated by Sall4a. Our study also showed that Bmi-1 could serve as a new therapeutic target for the treatment of pediatric ALL. The online version of this article (doi:10.1186/s12885-017-3049-3) contains supplementary material, which is available to authorized users.