Upregulation of the proto-oncogene Bmi-1 predicts a poor prognosis in pediatric acute lymphoblastic leukemia

• Published in: BMC cancer Vol. 17; no. 1; p. 76
• Main Authors: Peng, Hong-Xia, Liu, Xiao-Dan, Luo, Zi-Yan, Zhang, Xiao-Hong, Luo, Xue-Qun, Chen, Xiao, Jiang, Hua, Xu, Ling
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 25.01.2017; BioMed Central
• Subjects: Acute lymphocytic leukemia; Analysis; Biomarkers, Tumor - genetics; Bone marrow; Cancer; Cell cycle; Child; Child health; Child, Preschool; Children & youth; Disease-Free Survival; Female; Gene expression; Gene Expression Regulation, Leukemic; Genetic aspects; Health aspects; Humans; Infant; Leukemia; Lymphoma; Male; Medical prognosis; Pathogenesis; Pediatrics; Polycomb Repressive Complex 1 - genetics; Precursor Cell Lymphoblastic Leukemia-Lymphoma - diagnosis; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology; Prognosis; Remission (Medicine); Risk factors; Transcription Factors - genetics; Pediatric acute lymphoblastic leukemia; Sall4; Prognosis; Bmi-1
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-017-3049-3

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.