阿糖胞苷治疗急性髓系白血病的耐药机制研究进展

Advances in the mechanism of resistance to cytarabine therapy in acute myeloid leukemia

急性髓系白血病（acute myeloid leukemia,AML）是一种高度异质性的血液系统恶性肿瘤,以大量异常分化的髓系祖细胞在骨髓、血液或组织中克隆增殖浸润为主要特征[1]。AML在我国的年发病率为1.62/10万,占成人急性白血病的60%~70%[2]。阿糖胞苷（Ara-C）是一种核苷类似物,作为AML诱导和巩固治疗的常规药物,

Acute myeloid leukemia （AMIL） is a highly heterogeneous hematological malignancy characterized by the proliferation and infiltration of poorly differentiated hematopoietic cells in the bone marrow, blood and tis- sues. Cytarabine is a kind of nucleoside analogues mostly used in the induction and consolidation therapy of AML. High dose cytarabine proved to be more effective in killing leukemic cells while it also brought more adverse effect and resistance. Based on its metabolic pathways in vivo, researchers found that insufficient uptake of cytarabine into cells, decrease of activating enzymes and activated products,increase of inactivating enzymes and intracellular dCTP amount could be the cause of cytarabine resistance in AML. Further investigation on the potential enzymes and candidate genes has been carried out in order to improve complete remission rates, overall survival and disease free survival of AML. This article will review recent advances in the mechanism of resistance to cytarabine therapy in AML.