Naoe T, Tagawa Y, Kiyoi H, Kodera Y, Miyawaki S, Asou N, Kuriyama K, Kusumoto S, Shimazaki C, Saito K, Akiyama H, Motoji T, Nishimura M, Shinagawa K, Ueda R, Saito H, Ohno R
Department of Infectious Diseases, Nagoya University School of Medicine, Nagoya, Japan.
Leukemia. 2002 Feb;16(2):203-8. doi: 10.1038/sj.leu.2402361.
We investigated the prognostic significance of genetic polymorphism in glutathione-S transferase mu 1 (GSTM1), glutathione-S transferase theta 1 (GSTT1), NAD(P)H:quinone oxidoreductase (NQO1) and myeloperoxidase (MPO), the products of which are associated with drug metabolism as well as with detoxication, in 193 patients with de novo acute myeloid leukemia (AML) other than M3. Of the patients, 64.2% were either homozygous or heterozygous for GSTT1 (GSTT1(+)), while 35.8% showed homozygous deletions of GSTT1 (GSTT1(-)). The GSTT1(-) group had a worse prognosis than the GSTT1(+) group (P = 0.04), whereas other genotypes did not affect the outcome. Multivariate analysis revealed that GSTT1(-) was an independent prognostic factor for overall survival (relative risk: 1.53; P = 0.026) but not for disease-free survival of 140 patients who achieved complete remission (CR). The rate of early death after the initiation of chemotherapy was higher in the GSTT1(-) group than the GSTT1(+) group (within 45 days after initial chemotherapy, P = 0.073; within 120 days, P = 0.028), whereas CR rates and relapse frequencies were similar. The null genotype of GSTT1 might be associated with increased toxicity after chemotherapy.
我们研究了谷胱甘肽 - S转移酶μ1（GSTM1）、谷胱甘肽 - S转移酶θ1（GSTT1）、NAD（P）H：醌氧化还原酶（NQO1）和髓过氧化物酶（MPO）基因多态性的预后意义，这些基因的产物与药物代谢以及解毒相关。研究对象为193例非M3型的初发急性髓系白血病（AML）患者。其中，64.2%的患者GSTT1为纯合子或杂合子（GSTT1(+)），而35.8%的患者GSTT1表现为纯合缺失（GSTT1(-)）。GSTT1(-)组的预后比GSTT1(+)组差（P = 0.04），而其他基因型不影响预后。多因素分析显示，GSTT1(-)是总生存的独立预后因素（相对风险：1.53；P = 0.026），但对于140例达到完全缓解（CR）的患者的无病生存无影响。GSTT1(-)组化疗开始后的早期死亡率高于GSTT1(+)组（初始化疗后45天内，P = 0.073；120天内，P = 0.028），而CR率和复发频率相似。GSTT1的无效基因型可能与化疗后毒性增加有关。
