FPGS rs1544105 polymorphism is associated with treatment outcome in pediatric B-cell precursor acute lymphoblastic leukemia

• Published in: Cancer cell international Vol. 13; no. 1; p. 107
• Main Authors: Liu, Shu-Guang, Gao, Chao, Zhang, Rui-Dong, Jiao, Ying, Cui, Lei, Li, Wei-Jing, Chen, Zhen-Ping, Wu, Min-Yuan, Zheng, Hu-Yong, Zhao, Xiao-Xi, Yue, Zhi-Xia, Li, Zhi-Gang
• Format: Journal Article
• Language: English
• Published: England BioMed Central 29.10.2013; BioMed Central Ltd
• Subjects: Blood; Colorectal cancer; Confidence intervals; Drug therapy; Genes; Genotype & phenotype; Hematology; Leukemia; Medical prognosis; Patients; Pediatrics; Primary Research; R&D; Regression analysis; Research & development; Risk assessment; Statistical analysis; Survival analysis; Beijing China
• ISSN: 1475-2867; 1475-2867
• DOI: 10.1186/1475-2867-13-107

Folypolyglutamate synthase (FPGS) catalyzes the polyglutamation of folates and antifolates, such as methotrexate (MTX), to produce highly active metabolites. FPGS tag SNP rs1544105C > T is located in the gene promoter. The aim of the present study was to investigate the impact of rs1544105 polymorphism on the treatment outcome in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). This study enrolled 164 children with BCP-ALL. We genotyped the FPGS SNP rs1544105, and analyzed the associations between its genotypes and treatment outcome. We also examined FPGS mRNA levels by real-time PCR in 64 of the 164 children, and investigated the function of this polymorphism on gene expression. We found significantly poor relapse-free survival (RFS) (p = 0.010) and poor event-free survival (EFS) (p = 0.046) in carriers of CC genotype. Multivariable Cox regression analyses adjusted for possible confounding variables showed that, relative to the CT + TT genotypes, the CC genotype was an independent prognostic factor for poor RFS (hazard ratio [HR], 4.992.; 95% CI, 1.550-16.078; p = 0.007). No association was found between any toxicity and rs1544105 polymorphism. Quantitative PCR results showed that individuals with the T allele had lower levels of FPGS transcripts. Our study indicates that FPGS rs1544105C > T polymorphism might influence FPGS expression and affect treatment outcome in BCP-ALL patients.