自噬与急性早幼粒细胞白血病

Autophagy and Acute Promyelocytic Leukemia

急性早幼粒细胞白血病(APL)是急性髓性白血病的一种亚型,其分子特征是具有t(15;17)(q22;q21)染色体易位,并形成融合肿瘤蛋白,进而阻止早幼粒细胞分化成熟。全反式维甲酸(ATRA)和三氧化二砷(ATO)作为经典的治疗APL的药物,能够通过转录调节并激活泛素-蛋白酶体通路,促进融合肿瘤蛋白降解,发挥其临床抗白血病的功效。最近的研究发现,ATRA与ATO均能够诱导APL细胞自噬,且自噬在融合肿瘤蛋白降解及诱导早幼粒细胞分化中发挥至关重要的作用。我们简要综述近年来APL的研究进展及自噬在APL治疗中的作用。

Acute promyelocytic leukemia（APL） is a unique subtype of acute myeloid leukemia,which is charac-terized by expressed an oncogenic fusion protein as a result of t（15;17）（q22;q21） chromosome translocation.Thisfusion protein blocks the differentiation of promyelocytes at the promyelocytic stage and leads to leukemogenesis.As classical drugs for APL,all trans retinoic acid（ATRA） and arsenic trioxide（ATO） exert their therapeutic effectby regulating transcription and promoting the degradation of fusion protein through ubiquitin-proteasome system.Re-cently,several reports indicated that both ATRA and ATO also activate autophagy-lysosomal pathway.It＇s worthnoting that autophagy is likely to be critical for oncogenic fusion protein degradation.Here,we reviewed the re-search progress of APL and explored the role of autophagy in APL therapy.