4-Hydroxy phenyl Retinamide Preferentially Targets FLT3 Mutated Acute Myeloid Leukemia via ROS Induction and NF-κB Inhibition
作者机构：Department of Hematology/OncologyGuangzhou Women and Children's Medical CenterGuangzhou 510623China Institute of PediatricsGuangzhou Women and Children’s Medical CenterGuangzhou 510623China Department of PediatricsThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China Bioinspired Engineering and Biomechanics CenterXi'an Jiaotong UniversityXi'an 710049China
出 版 物：《Current Medical Science》 (当代医学科学（英文）)
年 卷 期：2020年第40卷第5期
页 面：810-816页
核心收录：
学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 0703[理学-化学] 100214[医学-肿瘤学] 10[医学]
基 金：This work was partially funded by the National Natural Science Foundation of China(No.81300401) St.Baldrick’s Foundation International Scholar(No.581580) Natural Science Foundation of Guangdong Province(No.2015A030313460) Guangzhou Women and Children’s Medical Center(No.IP-2008-001 and No.GCP-2019-006)
主 题：4-Hydroxyphenyl retinamide acute myeloid leukemia FLT3 mutations ROS induction NF-κB inhibition
摘 要：FMS-like tyrosine kinase 3(FLT3)mutation is strongly associated with poor prognosis in acute myeloid leukemia(AML).Though many FLT3 inhibitors have been developed for clinical application with 34%-56%complete remission rate,patients would develop resistance sooner or later after initial response to tyrosine kinase inhibitors(TKIs),such as *** increasing studies have shown that several resistance related mutations of FLT3 emerged during the AML ***,further investigation is warranted for these FLT3mu,AML patients to achieve a better treatment outcome.4-Hydroxyphenyl retinamide(4-HPR)has been investigated extensively in animal models and clinical trials as an anticancer/chemopreventive agent and is currently used for protection against cancer development/recurrence,with minimal side *** this study,we performed gene-set enrichment analysis and found that down-regulated genes induced by 4-HPR were associated with FLT3-ITD gene ***34+ AML stem/progenitor cells separated from 32 AML samples were treated with *** analysis showed that AML cells with FLT3-ITD genetic alteration were more sensitive to 4-HPR treatment than those without ***,we treated 22 primary AML cells with 4-HPR and found that 4-HPR was more toxic to AML cells with *** results indicated that 4-HPR was preferentially cytotoxic to all FLT3-ITD AML cells irrespective of stem/progenitor cells or blast cells.4-HPR-induced reactive oxygen species(ROS)production and NF-kB inhibition might be the reason of 4-HPR selectivity on FLT3 mutated AML cells.
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