Takanashi Mami, Morimoto Akira, Yagi Tomohito, Kuriyama Kikuko, Kano Gen, Imamura Toshihiko, Hibi Shigeyoshi, Todo Shinjiro, Imashuku Shinsaku
Department of Pediatrics, Kyoto Prefectural University of Medicine, Japan.
Haematologica. 2003 Nov;88(11):1238-44.
The glutathione-S-transferase (GST) polymorphism may affect the outcome of treatment of leukemia because GSTs play an important role in detoxifying the chemotherapeutic agents used to kill leukemia cells. However, results of previous reports have been controversial. This study was undertaken to clarify the influence of GST polymorphism on the outcome of childhood B-precursor acute lymphoblastic leukemia (ALL).
Eighty-two patients with childhood B-precursor ALL treated during 1988-1999 with our ALL protocol (median follow-up time 89.5 months, range 31 -169 months) were examined for GST gene patterns. The effect of GSTM1 and GSTT1 deletion genotypes on the clinical features and therapeutic results was analyzed.
All patients attained complete remission but 12 had an early relapse (within 30 months of the initiation of treatment). In univariate analysis, early relapse of ALL was correlated significantly with the presence of the t(9;22)(q34;q11) cytogenetic abnormality (p=0.0003), high white blood cell counts (p=0.015) and double null genotype (p=0.027). Multivariate analysis revealed that the GST double null genotype was the only significant independent predictor of early relapse (p=0.018).
The simultaneous deletion of both the GSTM1 and GSTT1 genes is more predictive than any other parameter of early relapse of childhood B-precursor ALL.
谷胱甘肽-S-转移酶（GST）基因多态性可能影响白血病的治疗结果，因为GST在用于杀死白血病细胞的化疗药物解毒过程中发挥重要作用。然而，既往报道的结果存在争议。本研究旨在阐明GST基因多态性对儿童B前体急性淋巴细胞白血病（ALL）治疗结果的影响。
对1988 - 1999年期间采用我们的ALL方案治疗的82例儿童B前体ALL患者（中位随访时间89.5个月，范围31 - 169个月）进行GST基因模式检测。分析GSTM1和GSTT1缺失基因型对临床特征和治疗结果的影响。
所有患者均获得完全缓解，但12例早期复发（治疗开始后30个月内）。单因素分析显示，ALL早期复发与t(9;22)(q34;q11)细胞遗传学异常（p = 0.0003）、高白细胞计数（p = 0.015）和双缺失基因型（p = 0.027）显著相关。多因素分析显示，GST双缺失基因型是早期复发的唯一显著独立预测因素（p = 0.018）。
GSTM1和GSTT1基因同时缺失比其他任何参数更能预测儿童B前体ALL的早期复发。
