阿糖胞苷代谢关键酶活性与儿童恶性血液肿瘤临床疗效的关系研究

Relationship between activities of key enzymes of Ara-C metabolism and clinical efficacy in children with hematopoietic malignancies

目的通过检测急性白血病（acute leukemia，AL）及非霍奇金淋巴瘤（aggressive non-Hodgkin’s lymphoma，NHL）患儿骨髓单个核细胞内阿糖胞苷（Ara-c），代谢关键酶——脱氧胞苷激酶（deoxycyfidine kinasekinase，DCK）胞苷脱氨酶（cytidine deaminase，CDA）活性，探索阿糖胞苷代谢关键酶活性与儿童恶性肿瘤临床疗效的关系。方法采用同位素3H—Cytidine做为放射底物检测32例患儿（ALL19例，AML9例，晚期NHL4例）骨髓单个细胞内DCK、CDA酶活性，统计分析各组患儿的检测结果。结果初发患儿DCK酶活性明显高于复发患儿（P〈0．05）。初发患儿CDA酶活性明显低于复发患儿（p〈0．05）。初发患儿cDA／DCK明显低于复发患儿（P〈0．05）。初发患儿ALL、AML、NHL中DCK酶活性来见显著差异（P〉0．05）。酶的活性与患儿年龄、性别未发现相关性（P〉0．05）。结论DCK活性增高，有利于Ara-C转化为具有活性的Ara-CTP。CDA活性增高，将促进Ara-C迅速降解，影响疗效。所以，初发与复发患儿DCK、cDA酶活性的显著差异（DCK活性降低和CDA活性增强），很可能是导致肿瘤复发的原因。因此，骨髓单个核细胞内DCK、CDA酶活性表达强弱与Ara—C的疗效密切相关。

Objective To study the relationship between the expression of key enzymes of Ara-C metabolism and the outcome of acute leukemia and non-Hodgkin lymphoma in children via detecting deoxycytidine kinase （DCK）and cytidine deaminase （CDA）kinase activity. Methods 3H-Cytidine was used to detect DCK and CDA activity from 19 leukemia patients with acute lymphoblastic leukemia （ALL） , 9 patients with acute myeloid leukaemia （AML） and 4 patients with non- Hodgkin lymphoma leukemia （NHL）. Results The enzyme activity of DCK in the newly diagnosed patients was significantly higher than that in the relapsed cases. But the enzyme activity of CDA in the new diagnosed patients of the study group was significantly lower than that in the relapsed cases. The similar results were also observed in the two groups when compared clinical outcome with the ratio of CDA and DCK. There was no difference of the enzyme activity of DCK in different types of new diagnosed patients （ALL, AML, NHL）. There was no correlations among enzyme activity, age, and sex. Conclusion Increasing DCK activity can promote Ara-C metabolism to Ara-CTP, but enhancing CDA activity can accelerate Ara-C degradation with interfering clinical efficacy. The results in the study showed that the lower expression of DCK and higher expression of CDA may be the reasons for relapse patients. Thus, there is a strong correlationship between the expression of DCK and CDA with the clinical outcome of hematopoietic malignancies in children.