Arnér E S
Medical Nobel Institute for Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Leuk Lymphoma. 1996 Apr;21(3-4):225-31. doi: 10.3109/10428199209067604.
The nucleoside analog 2-chlorodeoxyadenosine (CdA, Cladribine) is a chemotherapeutic agent for treatment of leukemias and lymphomas, most successfully used in hairy cell leukemia and B-cell chronic lymphocytic leukemia. CdA is phosphorylated intracellularly to its monophosphate derivative by the enzymes deoxycytidine kinase and deoxyguanosine kinase. Cell lines deficient in deoxycytidine kinase were shown to be resistant to CdA and a high deoxycytidine kinase level in combination with low 5'-nucleotidase has been proposed to partly explain the selectivity in CdA toxicity for lymphoid cells. In this report biochemical properties in CdA phosphorylation mediated by deoxycytidine kinase and deoxyguanosine kinase are reviewed and discussed in relation to the further metabolism of CdA 5'-monophosphate, the different possible mechanisms of action and the correlation with clinical response. It is concluded that much is known about the metabolism and mechanisms of action of CdA, but that the remarkable therapeutic effect in hairy cell leukemia has yet to be explicitly explained.
核苷类似物2-氯脱氧腺苷（CdA，克拉屈滨）是一种用于治疗白血病和淋巴瘤的化疗药物，最成功地应用于毛细胞白血病和B细胞慢性淋巴细胞白血病。CdA在细胞内被脱氧胞苷激酶和脱氧鸟苷激酶磷酸化为其单磷酸衍生物。缺乏脱氧胞苷激酶的细胞系对CdA具有抗性，有人提出高脱氧胞苷激酶水平与低5'-核苷酸酶相结合，可部分解释CdA对淋巴细胞毒性的选择性。在本报告中，将回顾和讨论由脱氧胞苷激酶和脱氧鸟苷激酶介导的CdA磷酸化的生化特性，以及与CdA 5'-单磷酸的进一步代谢、不同可能的作用机制和与临床反应的相关性。得出的结论是，关于CdA的代谢和作用机制已了解很多，但毛细胞白血病中显著的治疗效果尚未得到明确解释。
