Laboratoire de Pharmacocinétique, La Timone University Hospital of Marseille, UMR 911, Aix-Marseille University, Marseille, France.
Pharmacogenomics. 2012 Mar;13(4):393-7. doi: 10.2217/pgs.11.175.
We describe here the case of a 7-year old girl with lymphoma who developed life-threatening toxicities upon cytarabine plus mercaptopurine. Surprisingly, initial investigations on canonical thiopurine methyltransferase genetic polymorphism proved to be negative. We focused next on deregulations affecting the CDA gene implicated in the liver disposition of cytarabine. This patient was homozygous for both the 79A>C and the -31delC polymorphisms on the CDA gene and promoter, two genotypes with reported opposite effects on CDA phenotype. To determine the CDA status of this patient, additional functional testing was performed and eventually demonstrated that this patient was a poor metabolizer. This case demonstrates that besides affecting thiopurine methyltransferase, dysregulations with CDA should be screened to anticipate toxicities with the cytarabine plus mercaptopurine combination.
我们在此描述了一例 7 岁患有淋巴瘤的女孩，在使用阿糖胞苷联合巯嘌呤治疗时发生了危及生命的毒性反应。令人惊讶的是，最初针对经典的硫嘌呤甲基转移酶遗传多态性的研究结果呈阴性。我们接下来关注的是影响 CDA 基因的失调，该基因参与阿糖胞苷在肝脏中的处置。该患者在 CDA 基因及其启动子上均为 79A>C 和-31delC 两种多态性的纯合子，这两种基因型对 CDA 表型的影响相反。为了确定该患者的 CDA 状态，进行了额外的功能测试，最终证实该患者为代谢不良者。该病例表明，除了影响硫嘌呤甲基转移酶外，还应筛查 CDA 的失调情况，以预测阿糖胞苷联合巯嘌呤治疗的毒性反应。
