ABCB1基因多态性与中国急性髓系白血病患者蒽环类药物和阿糖胞苷预后的相关性
Association of ABCB1 polymorphisms with prognostic outcomes of anthracycline and cytarabine in Chinese patients with acute myeloid leukemia.
作者信息
He Hui, Yin Jiye, Li Xi, Zhang Yu, Xu Xiaojing, Zhai Ming, Chen Juan, Qian Chenyue, Zhou Honghao, Liu Zhaoqian
机构信息
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.
出版信息
Eur J Clin Pharmacol. 2015 Mar;71(3):293-302. doi: 10.1007/s00228-014-1795-6. Epub 2015 Jan 9.
PURPOSE
To investigate the influence of ABCB1 polymorphisms on prognostic outcomes in Chinese patients with de novo intermediate-risk acute myeloid leukemia (AML) and to examine the gene expression level in relation to the genetic variation.
METHODS
In total, 263 Chinese intermediate-risk AML patients treated with anthracycline and cytarabine were enrolled. G2677T, C1236T, and C3435T of the ABCB1 gene were analyzed by the allele-specific matrix-assisted laser desorption. Expression of ABCB1 messenger RNA (mRNA) was tested in 101 patients of known genotype and haplotype for ABCB1 polymorphisms. Basic clinical characteristics of these patients were collected from medical records.
RESULTS
Survival analysis showed that patients with AML (TTT haplotype) had a longer overall survival (OS) (p < 0.001, 29.2 months, 95 % confidence interval [CI], 26.9-31.5 months) and relapse-free survival (RFS) (p = 0.005, 21.8 months, 95 % CI, 19.5-24.0 months) compared with those without TTT haplotype (21.9 months, 95 % CI, 19.6-24.2 months; 16.5 months, 95 % CI, 14.6-18.5 months). After adjusting for age; gender; leukocyte count; hemoglobin level; platelet levels; French, American, and British classification; lactate dehydrogenase levels; Eastern Cooperative Oncology Group performance status; nucleophosmin gene; and fms-related tyrosine kinase 3 gene, the multivariate survival analysis showed that the TTT haplotype appeared to be a predicting factor for OS (p = 0.001, hazard ratio = 1.854, 95 % CI, 1.301-2.641) and RFS (p = 0.009, hazard ratio = 1.755, 95 % CI, 1.153-2.671). Moreover, a significant association between the TTT haplotype and relapse in AML patients was observed in this study (p = 0.002, odds ratio = 0.410, 95 % CI, 0.235-0.715). Gene expression level was significantly lower in patients with the TTT haplotype than in the patients with the other haplotypes (p = 0.004).
CONCLUSIONS
The findings suggested the TTT haplotype was possibly related to the OS, RFS, and relapse in Chinese patients with AML.
目的
探讨ABCB1基因多态性对中国初发中度危险急性髓系白血病（AML）患者预后的影响，并研究基因表达水平与基因变异的关系。
方法
共纳入263例接受蒽环类药物和阿糖胞苷治疗的中国中度危险AML患者。采用等位基因特异性基质辅助激光解吸电离技术分析ABCB1基因的G2677T、C1236T和C3435T位点。对101例已知ABCB1基因多态性基因型和单倍型的患者检测ABCB1信使核糖核酸（mRNA）的表达。从病历中收集这些患者的基本临床特征。
结果
生存分析显示，与无TTT单倍型的AML患者（总生存[OS]21.9个月，95%置信区间[CI]，19.6 - 24.2个月；无复发生存[RFS]16.5个月，95%CI，14.6 - 18.5个月）相比，具有TTT单倍型的患者有更长的OS（p < 0.001，29.2个月，95%CI，26.9 - 31.5个月）和RFS（p = 0.005，21.8个月，95%CI，19.5 - 24.0个月）。在调整年龄、性别、白细胞计数、血红蛋白水平、血小板水平、法国 - 美国 - 英国分类、乳酸脱氢酶水平、东部肿瘤协作组体能状态、核磷蛋白基因和fms相关酪氨酸激酶3基因后，多因素生存分析显示TTT单倍型似乎是OS（p = 0.001，风险比 = 1.854，95%CI，1.301 - 2.641）和RFS（p = 0.009，风险比 = 1.755，95%CI，1.153 - 2.671）的预测因素。此外，本研究观察到TTT单倍型与AML患者复发之间存在显著关联（p = 0.002，比值比 = 0.410，95%CI，0.235 - 0.715）。TTT单倍型患者的基因表达水平显著低于其他单倍型患者（p = 0.004）。
结论
研究结果提示TTT单倍型可能与中国AML患者的OS、RFS及复发有关。
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