摘要
目的探讨谷胱甘肽硫转移酶（GSTs）家族中GSTr1和GSTM1基因多态性与急性髓系白血病（AML）疗效，药物不良反应与预后的关系。方法AML患者180例，用多重PCR方法检测GSTr1和GSTM1基因型，比较不同基因型患者的诱导治疗完全缓解（CR）率，药物不良反应发生率，总体生存期，无复发生存期和复发率。结果（1）GSTr1和GSTM1基因双非缺失型（double—present型）患者一疗程CR率高于GSTr1，GSTM1任一基因缺失型（null型），二者差异有统计学意义（P=0．013）。GSTT1／GSTM1的nuH基因型患者发生不CR的危险度是double—present型患者的8．736倍（95％CI 1．146～66．574）。GSTT1 present型一疗程CR率高于GSTT1 null型，二者比较亦有统计学意义（P=0．021，OR=2．572，95％CI 1．136～5．826）；（2）GSTT1和GSTM1基因型分布与诱导治疗后中性粒细胞〈0．5×10^9／L及PLT〈20×10^9／L持续时间差异无统计学意义，GSTM1 null型患者发生AST异常的危险度是GSTM1 present型的2．593倍（P=0．016，95％CI 1．176～5．717）；（3）double—present型总体和无复发生存期较GSTT1／GSTM1的null型患者长（平均总体生存期为68．4、38．5个月，P=0．028；平均无复发生存期为73．5、34．9个月，P=0．014），GSTT1 null型患者无复发生存期短于GSTT1 present型患者（平均无复发生存期为26．7、64．3个月，P=0．038），但二者总体生存期无统计学意义（P=0．653）。double—present型患者复发率显著低于GSTT1／GSTM1的null型患者（13．3％、35．6％，P=0．019）。结论GSTT1，GSTMl基因型与AML患者治疗CR率、复发率、化疗的不良反应及预后均有显著相关性，GSTT1和GSTMl基因型有助于指导AML患者个体化治疗方案的制定。
Objective To investigate the impact of GSTT1 and GSTM1 genotypes on response, drug side effects and prognosis of acute myeloid leukemia（AML）. Methods GSTT1 and GSTM1 genotypes were analysed in 180 AML patients with PCR. Complete remission（CR） rate, drug side-effects, overall survival, relapse-free survival and relapse rate were compared in groups with or without GSTT1 and GSTM1 genes. Results （ 1 ） The CR rate （96. 9% ） in GSTT1 and GSTM1 genes double-present patients was significantly higher than that in patients of GSTT1 null or GSTM1 null（ CR rate 78.0% ） （ P = 0. 013 ）. The risk of failure to achieve CR in patients with GSTT1 nuU/GSTM1 null is 8. 736 times higher than that in patients with GSTT1 and GSTM1 genes double-present（ odds ratio OR was 8.736, 95% CI was 1. 146 - 66. 574）. The CR rate（88.4% ）in GSTT1 present patients was also significantly higher than that in patients of GSTT1 null （CR rate 74.7% ） （ P = 0. 021, OR = 2. 572, 95% CI 1. 136 - 5. 826 ）. （ 2 ） There was no significant relationship between GSTT1/GSTM1 genotypes and the lasting time of neutrophilic granulocyte（ANC） 〈 0. 5 × 10^9/L and PLT 〈 20 × 10^9/L. The risk of ALT abnormality in patients with GSTM1 null is 2. 593 times higher than that in patients with GSTM1 present（P =0. 016,95% C1 1. 176 -5.717）. （3）Overall survival and relapse-free survival of GSTT1 and GSTM1 double-present patients were significantly better than those in patients of GSTT1 null/GSTM 1 null （ mean overall survival was 68.4 months vs 38. 5 months, P = 0. 028, and mean relapse-free survival was 73.5 months vs 34. 9 months, P = 0.014, respectively）. Relapse-free survival in GSTT1 null patients was significantly shorter than that in patients with GSTT1 present （ 26. 7 months vs 64. 3 months,P =0. 038） , but there was no significant difference of overall survival between the two groups. The relapse rate of double-present patients was significantly lower than that of GSTT1 null/ GSTM1 null patients（13.3% vs 35.6%,P=0.019）. Conclusion GSTT1 and GSTM1 genotypes were apparently related with response, drug side effects and prognosis of patients with AML. GSTT1 and GSTM1 genotype might be useful in selecting appropriate chemotherapy regimens for patients with AML.
出处
《中华内科杂志》
CAS
CSCD
北大核心
2006年第3期213-216,共4页
Chinese Journal of Internal Medicine
基金
国家自然科学基金资助项目(30270573)
新世纪优秀人才支持计划资助项目
