胸苷酸合成酶基因多态性对儿童急性淋巴细胞白血病大剂量甲氨蝶呤相关毒性的影响

[Influence of thymidylate synthase gene polymorphisms on high-dose methotrexate-related toxicities in childhood acute lymphoblastic leukemia].

作者信息

Zhu Xiu-Juan, He Xiang-Ling, Wu Yan-Peng, Zou Run-Ying, Li Wan-Li, Zou Hui, You Ya-Lan, Liu Hua, Tian Xin

机构信息

Department of Pediatrics, First Affiliated Hospital of Hunan Normal University/Hunan Province People's Hospital, Changsha 410005, China.

出版信息

Zhongguo Dang Dai Er Ke Za Zhi. 2015 Jan;17(1):11-4.

PMID:25616285

Abstract

OBJECTIVE

To investigate the influence of thymidylate synthase (TS) gene polymorphisms on high-dose methotrexate (HD-MTX)-related toxicities in childhood acute lymphoblastic leukemia (ALL).

METHODS

A total of 73 children who were diagnosed with ALL between March 2011 and March 2013 were included into this study. Genomic DNAs were extracted from their peripheral blood. And then the genotypes of TS 5'-UTR were determined by direct DNA sequencing after PCR. The toxicity response of 73 patients receiving HD-MTX chemotherapy were observed and recorded, and plasma MTX concentrations at 42-48 hours after chemotherapy were measured.

RESULTS

The main HD-MTX-related toxicities of 73 patients receiving HD-MTX chemotherapy were neutropenia, decreased hemoglobin level, thrombocytopenia, liver toxicity, mucosal damage, and gastrointestinal reactions. There were no significant differences in the incidence rate of HD-MTX-related toxicities between children with different TS 5'-UTR genotypes after chemotherapy (P>0.05). TS 5'-UTR genotype was not significantly correlated with plasma MTX concentrations at 42-48 hours after chemotherapy (P>0.05).

CONCLUSIONS

TS gene polymorphisms have no influence on the incidence of HD-MTX-related toxicities in childhood ALL.

摘要

目的

探讨胸苷酸合成酶（TS）基因多态性对儿童急性淋巴细胞白血病（ALL）大剂量甲氨蝶呤（HD-MTX）相关毒性的影响。

方法

纳入2011年3月至2013年3月期间确诊为ALL的73例儿童。从其外周血中提取基因组DNA。然后通过PCR后直接DNA测序确定TS 5'-UTR的基因型。观察并记录73例接受HD-MTX化疗患者的毒性反应，并测定化疗后42 - 48小时的血浆甲氨蝶呤浓度。

结果

73例接受HD-MTX化疗患者的主要HD-MTX相关毒性为中性粒细胞减少、血红蛋白水平降低、血小板减少、肝毒性、黏膜损伤和胃肠道反应。化疗后不同TS 5'-UTR基因型儿童之间HD-MTX相关毒性的发生率无显著差异（P>0.05）。TS 5'-UTR基因型与化疗后42 - 48小时的血浆甲氨蝶呤浓度无显著相关性（P>0.0�）。