AHR signaling pathway reshapes the metabolism of AML/MDS cells and potentially leads to cytarabine resistance  

作　　者：Yan Jia Juan Guo Youshan Zhao Zheng Zhang Lei Shi Ying Fang Dong Wu Lingyun Wu Chunkang Chang 

机构地区：[1]Department of Hematology,Shanghai Jiao Tong University Affiliated Sixth People’s Hospital,Shanghai 200233,China

出　　处：《Acta Biochimica et Biophysica Sinica》2021年第4期492-500,共9页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grants from the National Natural Science Foundation of China(Nos.81570108 and 81400090).

摘　　要：Emerging evidence suggests that aryl hydrocarbon receptor(AHR)promotes the initiation,invasion,progression,and metastasis of cancer cells.However,its effects in patients with myelodysplastic syndrome/acute myeloid leukemia(MDS/AML)remain undefined.In this study,we aimed to investigate the effects of AHR activation on malignant cells in patients with MDS/AML.We found that AHR was expressed aberrantly in patients with MDS/AML.Further studies demonstrated that inhibiting AHR decreased the mitochondrial dehydrogenase content and the mitochondrial membrane potential(MMP)in MDS/AML cells.Activating AHR with L-kynurenine(Kyn)increased AHR expression,which was accompanied by an increase in mitochondrial dehydrogenase content and MMP in MDS/AML cells.Moreover,the expression level of mitochondria-associated mitochondrial transcription factor A was increased after activating AHR with L-Kyn when compared with that in the control group but decreased after inhibiting the AHR signal.Activating AHR in MDS/AML cells enhanced the resistance to cytarabine.These findings indicated that activating the AHR signaling pathway reshaped the metabolism in MDS/AML cells,thus contributing to the resistance to cytarabine.

关 键 词：AHR AML MDS mitochondrial metabolism RESISTANCE 

分 类 号：R96[医药卫生—药理学]