全反式维甲酸联合As_(2)O_(3)对初发急性早幼粒细胞白血病患者体内相关基因表达的影响

Effect of all-trans retinoic acid combined with As_(2)O_(3) on the expression of related genes in patients with primary acute promyelocytic leukemia

目的 研究全反式维甲酸联合三氧化二砷(As_(2)O_(3))对初发急性早幼粒细胞白血病(APL)患者体内相关基因表达的影响。方法 选择2014年3月-2017年6月首次在喀什地区第一人民医院诊断为APL的50例患者,根据治疗方案不同分为接受全反式维甲酸联合As_(2)O_(3)治疗的观察组24例,全反式维甲酸联合化疗的对照组26例。治疗前及治疗后14、28 d,测定骨髓中增殖、凋亡、侵袭相关基因的表达水平。结果 与治疗前比较,两组治疗后2周、4周时骨髓中增殖相关基因染色体10上缺失的磷酸酶与张力蛋白同源物基因(PTEN)、凋亡相关基因Bcl-2相关X蛋白(BAX)、高温需求蛋白A2(HtrA2)、含半胱氨酸的天冬氨酸蛋白水解酶-3(Caspase-3)、基质金属蛋白酶组织抑制因子(TIMP)1、TIMP2的mRNA表达水平升高,C-myc、细胞周期蛋白B1(CyclinB1)、周期蛋白依赖性激酶1(CDK1)、细胞FLICE样抑制蛋白(c FLIP)、生存素、侵袭相关基因基质金属蛋白酶(MMP)2、MMP9、CXC趋化因子受体(CXCR)4、CXCR7的mRNA表达水平降低,差异有统计学意义(P<0.05);观察组治疗后2周、4周时骨髓中PTEN、BAX、HtrA2、Caspase-3、TIMP1、TIMP2的mRNA表达水平均高于对照组,C-myc、CyclinB1、CDK1、cFLIP、生存素、MMP2、MMP9、CXCR4、CXCR7的mRNA表达水平均低于对照组,差异有统计学意义(P<0.05)。结论 全反式维甲酸联合As_(2)O_(3)治疗初发APL能够明显调控增殖、凋亡、侵袭相关基因的表达。

Objective To investigate the effect of all-trans retinoic acid combined with arsenic trioxide(As_(2)O_(3))on the expression of related genes in patients with primary acute promyelocytic leukemia(APL).Methods 50 patients who were first diagnosed with APL in Kashgar Prefecture First People’s Hospital between March 2014 and June 2017 were selected and divided into the observation group(24 cases)receiving all-trans retinoic acid combined with As_(2)O_(3) treatment and the control group(26 cases)receiving all-trans retinoic acid combined with chemotherapy.Expression levels of genes related to proliferation,apoptosis and invasion in bone marrow were determined before as well as 14 days and 28 days after treatment.Results Gompared with before treatment,phosphatase and tensin homolog deleted on chromosome 10(PTEN),Bcl-2 associated X protein(BAX),high temperature requirement protein A2(HtrA2),cysteinyl aspartate specific proteinase(Caspase-3),tissue inhibitor of metallo proteinase(TIMP)1 and TIMP2 mRNA expression levels in bone marrow of both groups significantly increased while C-myc,CyclinB1,cyclin-dependent kinases(CDK1),cellular FLICE-Like inhibitory protein(cFLIP),Survivin,matrix metallo proteinase(MMP)2,MMP9,CXC chemokine receptors(CXCR)4 and CXCR7 mRNA expression levels significantly decreased at 2 weeks and 4 weeks after treatment,the difference was statistically significant(P<0.05).Compared with control group at 2 weeks and 4 weeks after treatment,PTEN,BAX,HtrA2,Caspase-3,TIMP1 and TIMP2 mRNA expression levels in bone marrow of the observation group were significantly increased,while Cmyc,CyclinB1,CDK1,cFLIP,Survivin,MMP2,MMP9,CXCR4 and CXCR7 mRNA expression levels were significantly decreased,the difference was statistically significant(P<0.05).Conclusion All-trans retinoic acid combined with As_(2)O_(3) could significantly regulate the expression of genes related to proliferation,apoptosis and invasion in the treatment of primary acute promocytic leukemia.