KAT2A、CDK4/CDK6在儿童急性白血病患者中的表达及作用机制研究

Expression and Mechanism of KAT2A and CDK4/CDK6 in Children with Acute Leukemia

目的:探讨组蛋白乙酰转移酶2A(KAT2A)、细胞周期蛋白D1依赖激酶4/6(CDK4/CDK6)在儿童急性白血病患者中的表达及作用机制。方法:选择2017年6月-2018年11月收治的71例儿童急性白血病患者作为儿童急性白血病组;选择同期健康体检者59例作为对照组。采用实时荧光PCR技术(组蛋白修饰基因定量PCR)芯片测定2组组蛋白修饰基因表达和CDK4、CDK6及CDK4/CDK6 mRNA的表达水平;对KAT2A阳性表达者给予Western blot验证;采用SPSS Pearson相关性分析软件对儿童急性白血病患者KAT2A表达与CDK4、CDK6、CDK4/CDK6表达相关性进行分析。结果:通过对已有芯片数据进行综合分析,儿童急性白血病组KAT2A表达阳性为78.87%,明显高于对照组阳性率(8.47%)(P<0.05);儿童急性白血病组CDK4、CDK6 mRNA水平明显高于对照组(P<0.05);儿童急性白血病组CDK4/CDK6 mRNA表达水平明显低于对照组(P<0.05);Western blot结果表明,KAT2A、CDK4和CDK6在儿童急性白血病患者中表达水平高于对照组,而CDK4/CDK6表达水平低于对照组。SPSS Pearson相关性分析结果表明,儿童急性白血病患者KAT2A阳性表达率与CDK4、CDK6 mRNA表达水平呈正相关性(r=0.673,r=0.559),与CDK4/CDK6 mRNA表达水平呈负相关性(r=-0.762)。结论:KAT2A在儿童急性白血病患者中呈高表达,而CDK4/CDK6呈低表达,二者存在明显相关性,有望成为儿童急性白血病治疗新的靶点。

Objective:To investigate the expression and mechanism of histone acetyltransferase 2 A(KAT2 A)and cyclin D1 dependent kinase 4/6(CDK4/CDK6)in children with acute leukemia(AL).Methods:Seventy-one children with leukemia were selected from June 2017 to November 2018 and were enrolled in AL children group.59 persons of healthy physical examination were selected and enrolled in control group.Real-time fluorescent quantification PCR chip was used to determine the expression of histone-modified genes and the expression levels of CDK4,CDK6 and CDK4/CDK6 mRNA;Western blot was used to validated KAT2 A-positive expression;SPSS Pearson correlation analysis software was used to analyze the correlation between KAT2 A and CDK4/CDK6 expression in children with acute leukemia.Results:By comprehensive analysis of the existing chip data,the positive expression of KAT2 A in the AL children group was 78.87%,which was higher than that in the control group(8.47%)(P<0.05).The expression level of CDK4 and CDK6 mRNA in the AL children group was higher than that in the control group(P<0.05);the expression level of CDK4/CDK6 mRNA in the AL children group was lower than that in the control group(P<0.05).The results of Western blot showed that the expression levels of KAT2 A,CDK4 and CDK6 in AL children were higher than those in the control group,while the CDK4/CDK6 expression level in AL children group was lower than that in control group.The results of SPSS Pearson correlation analysis showed that the positive expression rate of KAT2 A in AL children group positively correlated with expression level of CDK4 and CDK6 mRNA(r=0.673,r=0.559),and negatively correlated with expression level of CDK4/CDK6 mRNA(r=-0.762).Conclusion:The KAT2 A is highly expressed in AL children,while the CDK4/CDK6 is lowly expressed in AL children,there is a significant correlationbetween of them,which is expected to become a new target for the treatment of acute leukemia children.