自噬在急性淋巴细胞白血病中作用的研究进展

Research progress on the role of autophagy in acute lymphoblastic leukemia

目的总结自噬在急性淋巴细胞白血病(ALL)发病、药物治疗及相关机制中的研究进展。方法以“自噬、急性淋巴细胞白血病、融合基因、治疗、进展”为中文关键词,以“autophagy,acute lymphoblastic leukemia,fusion gene,therapy,progress”为英文关键词,系统检索中国知网和PubMed数据库2010-01-01-2023-12-31发表的相关文献。纳入标准:(1)自噬及自噬发生的分子机制;(2)自噬与ALL融合基因突变发病中的关系;(3)自噬与ALL的关系及相关机制。排除标准:(1)会议、评论性及学位论文等;(2)内容关联性不强、结论尚存在争议及内容陈旧的文献。最终纳入66篇文献进行分析(中文4篇,英文62篇)。结果自噬相关蛋白在ALL患者中表达异常,且在不同的融合基因突变ALL中参与了ALL的发病及药物治疗过程,该过程可能与JAK/STAT、SIRT1/AMPK、NF-κB、cAMPK、c-Myc、Akt/mTOR/p70S6K/4E-BP1、PI3K/AKT/mTOR等分子和(或)信号通路相关。在ALL的不同治疗阶段,抑制或激活自噬与促进或抑制ALL的发生发展密切相关。结论自噬在维持细胞内环境的稳定发挥重要作用,参与了ALL的发病及治疗过程并在疾病不同阶段扮演了促进或抑制的双重作用,故探索有效靶向自噬的ALL个性化和(或)联合治疗方案至关重要。

Objective To summarize the research progress of the role of autophagy in the pathogenesis,drug therapy and related mechanisms of acute lymphoblastic leukemia(ALL).Methods With"autophagy,acute lymphoblastic leukemia,fusion gene,therapy,and progress"as the Chinese and English keywords,the relevant literature published on CNKI and PubMed databases from January 2010 to December 2023 were systematically searched.Inclusion criteria:(1)Autophagy and its molecular mechanism;(2)The relationship between autophagy and ALL fusion gene mutation;(3)The relationship between autophagy and ALL and its related mechanisms.Exclusion criteria:(1)Conferences,reviews and dissertations;(2)Literature with weak relevance,controversial conclusions and outdated contents.Finally,66 literature was included for analysis(4 in Chinese and 62 in English).Results Autophagy related proteins are abnormally expressed in ALL patients,and are involved in the pathogenesis and drug therapy of ALL in different fusion gene mutations.This process may be related to small molecules and/or signaling pathways such as JAK/STAT,SIRT1/AMPK,NF-κB,cAMPK,c-Myc,Akt/mTOR/p70S6K/4E-BP1,PI3K/AKT/mTOR.In different treatment stages of ALL,inhibition or activation of autophagy is closely related to promoting or inhibiting the occurrence and development of ALL.Conclusions Autophagy plays an important role in maintaining the stability of the intracellular environment,and is involved in the pathogenesis and treatment of ALL,and plays a dual role of promoting or inhibiting at different stages of the disease.Therefore,it is of great importance to explore effective autophagy targeting personalized and/or combination therapy for ALL.