急性淋巴细胞白血病硫嘌呤类药物耐药机制的研究进展

Research progresses of the mechanisms of thiopurine resistance in acute lymphoblastic leukemia

硫嘌呤类药物是急性淋巴细胞白血病(ALL)治疗缓解期的常用化学治疗药物之一,其在体内需经代谢转化成具有生物活性的巯基鸟嘌呤核苷酸,发挥杀死肿瘤细胞的作用。一旦硫嘌呤类药物在体内代谢通路中的关键酶存在单核苷酸多态性或发生功能突变,肿瘤细胞就会耐受硫嘌呤类药物而产生耐药复发。该文总结了ALL硫嘌呤类药物耐药相关代谢酶突变的研究进展,以期为克服其耐药提供新的思路和策略。

Thiopurine is one type of common chemotherapy drugs for the treatment of acute lymphoblastic leukemia （ALL） during remission. It must be metabolized and transformed to thioguanine nucleotides in vivo, which have the biological activity for killing tumor cells. Once key enzymes in thiopurine metabolic pathway develop single nucleotide polymorphisms or functional mutations, tumor cells will become resistant to thiopurine treatment and relapse will occur quickly. This article summarizes research progresses of metabolic enzyme mutations, which contribute to the thiopurine resistance in ALL, in order to provide novel ideas and strategies for overcoming the thiopurine resistance.