ACSL5,a prognostic factor in acute myeloid leukemia,modulates the activity of Wnt/β-catenin signaling by palmitoylation modification

查看全文 作　　者：Wenle [1,2]Ye;Jinghan [1,2]Wang;Jiansong [1,2]Huang;Xiao [3]He;Zhixin [4]Ma;Xia [1,2]Li;Xin [1,2]Huang;Fenglin [1,2]Li;Shujuan [1,2]Huang;Jiajia [1,2]Pan;Jingrui [1,2]Jin;Qing [1,2]Ling;Yungui [1,2]Wang;Yongping [5]Yu;Jie [1,2]Sun;Jie [1,2,6]Jin

机构地区：[1]Department of Hematology,The First Affiliated Hospital,Zhejiang University College of Medicine,Hangzhou 310003,China;[2]Key Laboratory of Hematopoietic Malignancies,Diagnosis and Treatment,Hangzhou 310009,China;[3]Research Centre,Centre hospitalier de l’Universitéde Montréal(CRCHUM),Montreal,Quebec H2L 4M1,Canada;[4]Women’s Hospital,School of Medicine,Zhejiang University,Hangzhou 310006,China;[5]Zhejiang Province Key Laboratory of Anti-Cancer Drug Research,College of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310058,China;[6]Cancer Center,Zhejiang University,Hangzhou 310058,China

出　　处：《Frontiers of Medicine》索引2023年第17卷第4期,共14页

基　　金：supported by the key international cooperation projects of the National Natural Science Foundation of China(No.81820108004);the major projects of the Zhejiang Provincial Department of Science and Technology(No.2021C03123);the Pediatric Leukemia Diagnosis and Therapeutic Technology Research Center of Zhejiang Province(No.JBZX-201904). 摘　　要：Acyl-CoA synthetase long chain family member 5(ACSL5),is a member of the acyl-CoA synthetases(ACSs)family that activates long chain fatty acids by catalyzing the synthesis of fatty acyl-CoAs.The dysregulation of ACSL5 has been reported in some cancers,such as glioma and colon cancers.However,little is known about the role of ACSL5 in acute myeloid leukemia(AML).We found that the expression of ACSL5 was higher in bone marrow cells from AML patients compared with that from healthy donors.ACSL5 level could serve as an independent prognostic predictor of the overall survival of AML patients.In AML cells,the ACSL5 knockdown inhibited cell growth both in vitro and in vivo.Mechanistically,the knockdown of ACSL5 suppressed the activation of the Wnt/β-catenin pathway by suppressing the palmitoylation modification of Wnt3a.Additionally,triacsin c,a pan-ACS family inhibitor,inhibited cell growth and robustly induced cell apoptosis when combined with ABT-199,the FDA approved BCL-2 inhibitor for AML therapy.Our results indicate that ACSL5 is a potential prognosis marker for AML and a promising pharmacological target for the treatment of molecularly stratified AML. 关键词：acute myeloid leukemia acyl-CoA synthetase long chain family member 5 WNT3A PALMITOYLATION ABT-199

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ACSL5,a prognostic factor in acute myeloid leukemia,modulates the activity of Wnt/β-catenin signaling by palmitoylation modification

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