骨髓增生异常综合征患者骨髓单个核细胞ASC和PLCG1表达及与疗效的关系

Expressions and significances of ASC and PLCG1in bone marrow mononuclear cells of patients with myelodysplastic syndrome

目的观察骨髓增生异常综合征(myelodysplastic syndrome,MDS)患者骨髓单个核细胞ASC和PLCG1表达变化,探讨二者与MDS患者临床特征及疗效的关系。方法MDS患者53例为MDS组,营养性贫血患者39例为对照组,入院后均行骨髓穿刺采集骨髓液,采用实时荧光定量PCR法检测骨髓单个核细胞ASC、PLCG1mRNA相对表达量。MDS患者依据指南规范治疗,治疗4个疗程后进行疗效评价,计算总有效率。比较MDS组与对照组、不同临床特征MDS患者骨髓单个核细胞ASC、PLCG1mRNA相对表达量。分别以ASC、PLCG1mRNA相对表达量中位数为界,将53例MDS患者分为ASC高表达组27例和ASC低表达组26例,PLCG1高表达组28例和低表达组25例,比较ASC及PLCG1高、低表达组总有效率。采用多因素logistic回归分析MDS患者规范治疗无效的影响因素。结果MDS组骨髓单个核细胞ASC mRNA相对表达量(2.41±0.29)高于对照组(1.31±0.31)(t=17.605,P<0.001),PLCG1mRNA相对表达量(1.46±0.35)低于对照组(2.75±0.29)(t=18.936,P<0.001)。IPSS-R评分高危、染色体核型复杂的MDS患者骨髓单个核细胞ASC mRNA相对表达量(2.89±0.33、2.81±0.27)分别高于IPSS-R评分中低危、染色体核型简单者(2.01±0.25、2.05±0.29)(t=11.041,P<0.001;t=9.837,P<0.001),PLCG1mRNA相对表达量(1.01±0.39、1.14±0.38)分别低于IPSS-R评分中低危、染色体核型简单者(1.83±0.33、1.75±0.30)(t=8.293,P<0.001;t=6.520,P<0.001);不同性别、年龄、MDS分型者骨髓单个核细胞ASC、PLCG1mRNA相对表达量比较差异均无统计学意义(P>0.05)。ASC高表达组总有效率(48.15%)低于ASC低表达组(84.62%)(χ^(2)=7.854,P=0.005),PLCG1低表达组总有效率(52.00%)低于PLCG1高表达组(78.57%)(χ^(2)=4.158,P=0.041)。染色体核型复杂(OR=2.643,95%CI:1.158~6.032,P=0.002)、IPSS-R评分高危(OR=1.630,95%CI:1.034~2.499,P=0.035)及骨髓单个核细胞ASC(OR=1.842,95%CI:1.060~3.202,P=0.020)、PLCG1(OR=0.846,95%CI:0.731~0.980,P=0.014)mRNA相对表达量是MDS患者规范治疗无效的影响因素。结论MDS患者骨髓单个核细胞ASC表达升高、PLCG1表达降低,染色体核型复杂、IPSS-R评分高危及骨髓单个核细胞ASC高表达、PLCG1低表达的MDS患者规范治疗的疗效差。

Objective To observe the changes of ASC and PLCG1expressions in bone marrow mononuclear cells of patients with myelodysplastic syndrome(MDS),and to investigate their relationships with the clinical characteristics and therapeutic efficacy.Methods Fifty-three MDS patients(MDS group)and 39nutritional anemia patients(control group)received bone marrow aspiration to harvest marrow fluid.The relative expressions of ASC and PLCG1in bone marrow mononuclear cells were detected by real-time fluorescence quantitative PCR.According to the treatment guidance for MDS,the efficacy was evaluated after 4cycles and the total effective rate was calculated.The relative expressions of ASC and PLCG1mRNAs were compared between two groups and among MDS patients with different clinical characteristics.Taking the medium relative expressions of ASC and PLCG1mRNAs as cut-off values,53patients were divided into highly expressed ASC group(n=27)and lowly expressed ASC group(n=26),as well as highly expressed PLCG1group(n=28)and lowly expressed PLCG1group(n=25).The total effective rates were compared between highly and lowly expressed ASC and PLCG1groups.Multivariate logistic regression analysis was done to evaluate the influencing factors of the failure of standard treatment in MDS patients.Results The relative expression of ASC mRNA was higher in MDS group(2.41±0.29)than that in control group(1.31±0.31)(t=17.605,P<0.001),while the relative expression of PLCG1mRNA was lower in MDS group(1.46±0.35)than that in control group(2.75±0.29)(t=18.936,P<0.001).The relative expressions of ASC mRNA were higher in MDS patients with high-risk IPSS-R score and complex karyotype(2.89±0.33,2.81±0.27)than those in patients with moderate low-risk IPSS-R score and simple karyotype(2.01±0.25,2.05±0.29)(t=11.041,P<0.001;t=9.837,P<0.001),and the relative expressions of PLCG1mRNA were lower in MDS patients with high-risk IPSS-R score and complex karyotype(1.01±0.39,1.14±0.38)than those in patients with moderate low-risk IPSS-R score and simple karyotype(1.83±0.33,1.75±0.30)(t=8.293,P<0.001;t=6.520,P<0.001).There were no significant differences in the relative expressions of ASC and PLCG1mRNAs in patients with different genders,ages and MDS types(P>0.05).The total effective rate was lower in highly expressed ASC group(48.15%)than that in lowly expressed ASC group(84.62%)(χ^(2)=7.854,P=0.005),and higher in highly expressed PLCG1group(78.57%)than that in lowly expressed PLCG1 group(52.00%)(χ^(2)=4.158,P=0.041).Complex karyotype(OR=2.643,95%CI:1.158-6.032,P=0.002),high-risk IPSS-R score(OR=1.630,95%CI:1.034-2.499,P=0.035),relative expression of ASC mRNA(OR=1.842,95%CI:1.060-3.202,P=0.020),and relative expression of PLCG1mRNA(OR=0.846,95%CI:0.731-0.980,P=0.014)were the influencing factors of the failure of standard treatment in MDS patients.Conclusion ASC increases and PLCG1decreases in MDS patients,and the complex karyotype,high-risk IPSS-R score,high expression of ASC and low expression of PLCG1in bone marrow mononuclear cells indicate a poor efficacy of standard treatment of MDS patients.