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Dual Inhibition of AKT/FLT3-ITD by A674563 Overcomes FLT3 Ligand-Induced Drug Resistance in FLT3-ITD positive AML

文献类型：期刊论文

作者Wang, Aoli1,2; Wu, Hong1,2; Chen, Cheng1,3; Hu, Chen1,3; Qi, Ziping1,3; Wang, Wenchao1,3; Yu, Kailin1; Liu, Xiaochuan1,2; Zou, Fengming1,3; Zhao, Zheng1,3
刊名ONCOTARGET
出版日期2016-05-17
卷号7期号:20页码:29131-29142
关键词Acute Myeloid Leukemia Flt3-itd Akt A6745763 Flt3-ligand
DOI10.18632/oncotarget.8675
文献子类Article
英文摘要The FLT3-ITD mutation is one of the most prevalent oncogenic mutations in AML. Several FLT3 kinase inhibitors have shown impressive activity in clinical evaluation, however clinical responses are usually transient and clinical effects are rapidly lost due to drug resistance. One of the resistance mechanisms in the AML refractory patients involves FLT3-ligand induced reactivation of AKT and/or ERK signaling via FLT3 wt kinase. Via a screen of numerous AKT kinase inhibitors, we identified the well-established orally available AKT inhibitor, A674563, as a dual suppressor of AKT and FLT3-ITD. A674563 suppressed FLT3-ITD positive AML both in vitro and in vivo. More importantly, compared to other FLT3 inhibitors, A674563 is able to overcome FLT3 ligand-induced drug resistance through simultaneous inhibition of FLT3-ITD- and AKT-mediated signaling. Our findings suggest that A674563 might be a potential drug candidate for overcoming FLT3 ligand-mediated drug resistance in FLT3-ITD positive AML.
WOS关键词ACUTE MYELOID-LEUKEMIA ; KINASE INHIBITOR ; IN-VIVO ; PROGRESS ; POTENT
WOS研究方向Oncology ; Cell Biology
语种英语
WOS记录号WOS:000377742600030
资助机构Scientific Research Grant of Hefei Science Center of CAS (SRG-HSC)(2015SRG-HSC022) ; Scientific Research Grant of Hefei Science Center of CAS (SRG-HSC)(2015SRG-HSC022) ; Scientific Research Grant of Hefei Science Center of CAS (SRG-HSC)(2015SRG-HSC022) ; Scientific Research Grant of Hefei Science Center of CAS (SRG-HSC)(2015SRG-HSC022) ; Scientific Research Grant of Hefei Science Center of CAS (SRG-HSC)(2015SRG-HSC022) ; Scientific Research Grant of Hefei Science Center of CAS (SRG-HSC)(2015SRG-HSC022) ; Scientific Research Grant of Hefei Science Center of CAS (SRG-HSC)(2015SRG-HSC022) ; Scientific Research Grant of Hefei Science Center of CAS (SRG-HSC)(2015SRG-HSC022) ; Chinese Academy of Sciences ; Chinese Academy of Sciences ; Chinese Academy of Sciences ; Chinese Academy of Sciences ; Chinese Academy of Sciences ; Chinese Academy of Sciences ; Chinese Academy of Sciences ; Chinese Academy of Sciences ; Anhui Province Natural Science Foundation Annual Key Program(1301023011) ; Anhui Province Natural Science Foundation Annual Key Program(1301023011) ; Anhui Province Natural Science Foundation Annual Key Program(1301023011) ; Anhui Province Natural Science Foundation Annual Key Program(1301023011) ; Anhui Province Natural Science Foundation Annual Key Program(1301023011) ; Anhui Province Natural Science Foundation Annual Key Program(1301023011) ; Anhui Province Natural Science Foundation Annual Key Program(1301023011) ; Anhui Province Natural Science Foundation Annual Key Program(1301023011) ; China "Thousand Talents Program" ; China "Thousand Talents Program" ; China "Thousand Talents Program" ; China "Thousand Talents Program" ; China "Thousand Talents Program" ; China "Thousand Talents Program" ; China "Thousand Talents Program" ; China "Thousand Talents Program" ; Scientific Research Grant of Hefei Science Center of CAS (SRG-HSC)(2015SRG-HSC022) ; Scientific Research Grant of Hefei Science Center of CAS (SRG-HSC)(2015SRG-HSC022) ; Scientific Research Grant of Hefei Science Center of CAS (SRG-HSC)(2015SRG-HSC022) ; Scientific Research Grant of Hefei Science Center of CAS (SRG-HSC)(2015SRG-HSC022) ; Scientific Research Grant of Hefei Science Center of CAS (SRG-HSC)(2015SRG-HSC022) ; Scientific Research Grant of Hefei Science Center of CAS (SRG-HSC)(2015SRG-HSC022) ; Scientific Research Grant of Hefei Science Center of CAS (SRG-HSC)(2015SRG-HSC022) ; Scientific Research Grant of Hefei Science Center of CAS (SRG-HSC)(2015SRG-HSC022) ; Chinese Academy of Sciences ; Chinese Academy of Sciences ; Chinese Academy of Sciences ; Chinese Academy of Sciences ; Chinese Academy of Sciences ; Chinese Academy of Sciences ; Chinese Academy of Sciences ; Chinese Academy of Sciences ; Anhui Province Natural Science Foundation Annual Key Program(1301023011) ; Anhui Province Natural Science Foundation Annual Key Program(1301023011) ; Anhui Province Natural Science Foundation Annual Key Program(1301023011) ; Anhui Province Natural Science Foundation Annual Key Program(1301023011) ; Anhui Province Natural Science Foundation Annual Key Program(1301023011) ; Anhui Province Natural Science Foundation Annual Key Program(1301023011) ; Anhui Province Natural Science Foundation Annual Key Program(1301023011) ; Anhui Province Natural Science Foundation Annual Key Program(1301023011) ; China "Thousand Talents Program" ; China "Thousand Talents Program" ; China "Thousand Talents Program" ; China "Thousand Talents Program" ; China "Thousand Talents Program" ; China "Thousand Talents Program" ; China "Thousand Talents Program" ; China "Thousand Talents Program"
源URL[http://ir.hfcas.ac.cn:8080/handle/334002/22448]  
专题合肥物质科学研究院_中科院强磁场科学中心
作者单位1.Chinese Acad Sci, High Field Magnet Lab, Hefei 230031, Anhui, Peoples R China
2.Univ Sci & Technol China, Hefei 230036, Anhui, Peoples R China
3.CHMFL HCMTC Target Therapy Joint Lab, Hefei 230031, Anhui, Peoples R China
4.Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA
5.Hefei Cosource Med Technol Co LTD, Hefei 230031, Anhui, Peoples R China
6.Chinese Acad Sci, Hefei Sci Ctr, Hefei 230031, Anhui, Peoples R China
推荐引用方式
GB/T 7714		 Wang, Aoli,Wu, Hong,Chen, Cheng,et al. Dual Inhibition of AKT/FLT3-ITD by A674563 Overcomes FLT3 Ligand-Induced Drug Resistance in FLT3-ITD positive AML[J]. ONCOTARGET,2016,7(20):29131-29142.
APA Wang, Aoli.,Wu, Hong.,Chen, Cheng.,Hu, Chen.,Qi, Ziping.,...&Liu, Qingsong.(2016).Dual Inhibition of AKT/FLT3-ITD by A674563 Overcomes FLT3 Ligand-Induced Drug Resistance in FLT3-ITD positive AML.ONCOTARGET,7(20),29131-29142.
MLA Wang, Aoli,et al."Dual Inhibition of AKT/FLT3-ITD by A674563 Overcomes FLT3 Ligand-Induced Drug Resistance in FLT3-ITD positive AML".ONCOTARGET 7.20(2016):29131-29142.

入库方式： OAI收割

来源：合肥物质科学研究院

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