Augmenter of liver regeneration promotes drug resistance of acute lymphoblastic leukemia through the alteration of mitochondrial functions and the inhibition of the mitochondrial apoptosis pathway

作者全名："Zhou, Jingwen; Zhou, Ying; Yuan, Shiyi; Li, Yifei; Xiao, Wenrui; Zhang, Ping; Lou, Shifeng; Shen, Yan"

作者地址："[Zhou, Jingwen; Zhou, Ying; Yuan, Shiyi; Li, Yifei; Xiao, Wenrui; Zhang, Ping; Lou, Shifeng; Shen, Yan] Chongqing Med Univ, Affiliated Hosp 2, Hematol Lab, Chongqing, Peoples R China; [Lou, Shifeng; Shen, Yan] Chongqing Med Univ, Affiliated Hosp 2, Hematol Lab, Chongqing 400010, Peoples R China"

通信作者："Lou, SF; Shen, Y (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Hematol Lab, Chongqing 400010, Peoples R China."

来源：EUROPEAN JOURNAL OF HAEMATOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001016537700001

JCR分区：Q2

影响因子：2.3

年份：2023

卷号：111

期号：2

开始页：279

结束页：292

文献类型：Article

关键词：ALR; drug resistance; mitochondria; mitochondrial apoptosis pathway; T-cell acute lymphoblastic leukemia

摘要："Background: Acute T lymphoblastic leukemia (T-ALL) occurs in 25% of adults diagnosed with Acute lymphocytic leukemia (ALL), and drug resistance is still a clinical obstacle. Augmenter of liver regeneration ( ALR) is important to ALL drug resistance and is involved in the regulation of mitochondrial function; we speculated that the high expression of ALR in T-ALL promotes drug resistance through the alteration of mitochondrial function and the inhibition of the mitochondrial apoptosis pathway. Method: We silenced and overexpressed ALR in the T-ALL cell lines that were untreated or treated with dexamethasone (DXM) or methotrexate (MTX). Apoptosis, proliferation, reactive oxygen species and ATP productions, mitochondrial membrane potential, and mitochondrial respiratory chain complex expression in cells were examined. The data were collated to comprehensively evaluate the effects of ALR expression change on mitochondrial function and drug resistance in T-ALL cells. Results: ALR knockdown led to the inhibition of proliferation, an increase in apoptosis, and the promotion of the cells' sensitivity to drugs. It also showed mitochondrial dysfunction. ALR knockdown actived the mitochondrial apoptosis pathway. The treatment of ALR knockdown T-ALL cells with MTX or DXM further altered the mitochondrial function of T-ALL cells and actived the mitochondrial apoptosis pathway. Overexpression of ALR promoted cell proliferation and drug resistance, reduced apoptosis, protected mitochondrial function, and inhibited the mitochondrial apoptosis pathway. Conclusion: T-ALL resistance caused by ALR through the alteration of mitochondrial function is associated with the inhibition of the mitochondrial apoptosis pathway."

基金机构：Chongqing Municipal Public Health Bureau; Chongqing People's Municipal Government [2020FYYX227]

基金资助正文："Chongqing Municipal Public Health Bureau, Chongqing People's Municipal Government, Grant/Award Number: 2020FYYX227"