阿糖胞苷代谢关键酶基因在儿童恶性血液肿瘤中的表达

目的通过检测儿童急性白血病(AL)及非霍奇金淋巴瘤(NHL)骨髓细胞内阿糖胞苷(Ara-C)代谢关键酶———脱氧胞苷激酶(DCK)和胞苷脱氨酶(CDA)的基因表达及酶活性水平,探索DCK和CDA表达与临床疗效的关系。方法共计31例患儿,其中初诊27例(ALL20例,AML3例,NHL4例),复发4例(ALL2例,AML、NHL各1例),采集患儿骨髓细胞,采用荧光定量PCR检测细胞内DCK、CDA基因表达,核素液闪法检测细胞内DCK、CDA酶活性,统计分析各组患儿的检测结果。结果 (1)DCK:ALL和NHL患儿DCK mRNA与酶活性水平均明显高于AML患儿(P0.05);初治患儿均明显高于复发患儿(P0.05);(2)CDA:AML和复发患儿的CDA酶活性水平明显高于ALL、NHL和初治患儿(P0.05),但各组病例间的CDA mRNA表达差异无显著性(P0.05)。(3)DCK和CDAmRNA表达与酶活性水平呈高度正相关。结论 AML以及某些复发的血液肿瘤患儿,其总体DCK酶活性及基因表达水平降低,CDA酶活性水平增高。DCK和CDA酶活性可能与儿童恶性血液肿瘤疗效相关。

The expression of Ara-C metabolism key enzymes in childhood hematopoietic malignancies

Objective To study the relationship between Ara-C metabolism key enzymes expression and the outcome of childhood hematopoietic malignancies by detecting deoxycytidine kinase(DCK)and cytidine deaminase(CDA)genes expression and kinase activityies.Methods Thirty-one children with hematopoietic malignancies were enrolled in this study.There were 27 newly diagnosed patients(20 cases of ALL,3 of AML and 4 of NHL),and 4 relapsed cases(2 cases of ALL,1 of AML and 1 of NHL).SYBR Green Realtime PCR and deoxy——cytidine were used to detect the expression and kinase activities of DCK and CDA in bone marrow for analysing the differences in different kinds of childhood hematopoietic malignancies.Results ① Both gene expression and kinase activity of DCK in ALL and NHL were significantly higher than that in AML(P<0.05).Besides,they were also higher in newly diagnosed cases than that in relapsed group.② CDA enzyme activity was significantly higher in AML and relapsed patients than that in ALL,NHL and newly diagnosed cases(P<0.05).However,there was no difference of CDA expression between these groups(P>0.05).③ Highly correlation between mRNA levels and enzyme activities were found in DCK and CDA.Conclusion AML and relapsed cases of childhood hematopoietic malignancies had lower DCK and higher CDA kinase activities,which may be associated with the outcome of the patients.