title: Upregulation of the proto-oncogene Bmi-1 predicts a poor prognosis in pediatric acute lymphoblastic leukemia.
abstract: 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.
authors.affiliation: Department of Hematology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, Guangdong, 510623, China.
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Peng
authors.affiliation: Division of Birth Cohort Study, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
authors.forename: Xiao-Dan
authors.initials: XD
authors.lastname: Liu
authors.affiliation: Department of Hematology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, Guangdong, 510623, China.
authors.forename: Zi-Yan
authors.initials: ZY
authors.lastname: Luo
authors.affiliation: Department of Hematology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, Guangdong, 510623, China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Xue-Qun
authors.initials: XQ
authors.lastname: Luo
authors.affiliation: Department of Pediatrics, Zhuzhou Central Hospital, Zhuzhou, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Hematology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, Guangdong, 510623, China. jiang_hua18@sina.cn.
authors.forename: Hua
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Hematology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, Guangdong, 510623, China. luoxul64@126.com.
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007223:Infant; D008297:Male; D063150:Polycomb Repressive Complex 1 / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C069077:BMI1 protein, human; D014408:Biomarkers, Tumor; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C472575:SALL4 protein, human; D014157:Transcription Factors; D063150:Polycomb Repressive Complex 1
keywords: Bmi-1; Pediatric acute lymphoblastic leukemia; Prognosis; Sall4