自噬在急性髓系白血病靶向治疗中的作用。
The role of autophagy in targeted therapy for acute myeloid leukemia.
机构信息
Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
出版信息
Autophagy. 2021 Oct;17(10):2665-2679. doi: 10.1080/15548627.2020.1822628. Epub 2020 Sep 22.
Although molecular targeted therapies have recently displayed therapeutic effects in acute myeloid leukemia (AML), limited response and acquired resistance remain common problems. Numerous studies have associated autophagy, an essential degradation process involved in the cellular response to stress, with the development and therapeutic response of cancers including AML. Thus, we review studies on the role of autophagy in AML development and summarize the linkage between autophagy and several recurrent genetic abnormalities in AML, highlighting the potential of capitalizing on autophagy modulation in targeted therapy for AML.: AML: acute myeloid leukemia; AMPK: AMP-activated protein kinase; APL: acute promyelocytic leukemia; ATG: autophagy related; ATM: ATM serine/threonine kinase; ATO: arsenic trioxide; ATRA: all trans retinoic acid; BCL2: BCL2 apoptosis regulator; BECN1: beclin 1; BET proteins, bromodomain and extra-terminal domain family; CMA: chaperone-mediated autophagy; CQ: chloroquine; DNMT, DNA methyltransferase; DOT1L: DOT1 like histone lysine methyltransferase; FLT3: fms related receptor tyrosine kinase 3; FIS1: fission, mitochondrial 1; HCQ: hydroxychloroquine; HSC: hematopoietic stem cell; IDH: isocitrate dehydrogenase; ITD: internal tandem duplication; KMT2A/MLL: lysine methyltransferase 2A; LSC: leukemia stem cell; MDS: myelodysplastic syndromes; MTORC1: mechanistic target of rapamycin kinase complex 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; NPM1: nucleophosmin 1; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; PML: PML nuclear body scaffold; ROS: reactive oxygen species; RB1CC1/FIP200: RB1 inducible coiled-coil 1; SAHA: vorinostat; SQSTM1: sequestosome 1; TET2: tet methylcytosine dioxygenase 2; TKD: tyrosine kinase domain; TKI: tyrosine kinase inhibitor; TP53/p53: tumor protein p53; ULK1: unc-51 like autophagy activating kinase 1; VPA: valproic acid; WDFY3/ALFY: WD repeat and FYVE domain containing 3.
尽管分子靶向治疗在急性髓细胞白血病 (AML) 中近期显示出治疗效果，但有限的反应和获得性耐药仍然是常见问题。许多研究将自噬与癌症的发展和治疗反应联系起来，包括 AML，自噬是一种涉及细胞对压力反应的基本降解过程。因此，我们综述了自噬在 AML 发生发展中的作用，并总结了自噬与 AML 中几种常见遗传异常之间的联系，强调了利用自噬调节作用来进行 AML 的靶向治疗的潜力。：AML：急性髓细胞白血病；AMPK：AMP 激活的蛋白激酶；APL：急性早幼粒细胞白血病；ATG：自噬相关；ATM：ATM 丝氨酸/苏氨酸激酶；ATO：三氧化二砷；ATRA：全反式维甲酸；BCL2：B 细胞淋巴瘤 2 凋亡调节因子；BECN1：自噬相关蛋白 1；BET 蛋白，溴结构域和末端外结构域家族；CMA：伴侣介导的自噬；CQ：氯喹；DNMT，DNA 甲基转移酶；DOT1L：DOT1 样组蛋白赖氨酸甲基转移酶；FLT3：fms 相关受体酪氨酸激酶 3；FIS1：分裂，线粒体 1；HCQ：羟氯喹；HSC：造血干细胞；IDH：异柠檬酸脱氢酶；ITD：内部串联重复；KMT2A/MLL：赖氨酸甲基转移酶 2A；LSC：白血病干细胞；MDS：骨髓增生异常综合征；MTORC1：雷帕霉素靶蛋白激酶复合物 1；MAP1LC3/LC3：微管相关蛋白 1 轻链 3；NPM1：核磷蛋白 1；PIK3C3/VPS34：磷脂酰肌醇 3-激酶催化亚单位 3；PML：PML 核体支架；ROS：活性氧；RB1CC1/FIP200：RB1 诱导卷曲螺旋 1；SAHA：伏立诺他；SQSTM1：自噬相关蛋白 1；TET2：tet 甲基胞嘧啶双加氧酶 2；TKD：酪氨酸激酶结构域；TKI：酪氨酸激酶抑制剂；TP53/p53：肿瘤蛋白 p53；ULK1：UNC-51 样自噬激活激酶 1；VPA：丙戊酸；WDFY3/ALFY：WD 重复和 FYVE 结构域包含 3。
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