SH3BGRL as a novel prognostic biomarker is down-regulated in acute myeloid leukemia

被引:15
作者
Xu, Limei [1 ,2 ]
Zhang, Mingming [2 ]
Li, Hui [2 ]
Guan, Wen [2 ]
Liu, Bin [2 ]
Liu, Fengqi [1 ]
Wang, Hehua [1 ]
Li, Juan [1 ]
Yang, Shulan [3 ]
Tong, Xiuzhen [1 ]
Wang, Haihe [2 ,4 ,5 ]
机构
[1] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Hematol, Guangzhou, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Zhongshan Sch Med, Dept Biochem, Guangzhou, Guangdong, Peoples R China
[3] Sun Yat Sen Univ, Affiliated Hosp 1, Ctr Translat Med, Guangzhou, Guangdong, Peoples R China
[4] Sun Yat Sen Univ, Ctr Stem Cell Biol & Tissue Engn, Key Lab, Minist Educ, Guangzhou, Guangdong, Peoples R China
[5] Sun Yat Sen Univ, Guangdong Engn & Technol Res Ctr Dis Model Anim, Guangzhou, Guangdong, Peoples R China
基金
美国国家科学基金会;
关键词
Acute myeloid leukemia; SH3BGRL; apoptosis; drug resistance; cell proliferation; PHOSPHATASE PRL-3; GENE; IDENTIFICATION; EXPRESSION; METASTASIS; MUTATIONS; PROMOTES; FLT3-ITD; COMPLEX; MARKERS;
D O I
10.1080/10428194.2017.1344843
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Phosphatase PRL-3 expression is positively associated to acute myeloid leukemia (AML) progression and drug resistance. SH3-domain-binding glutamic acid-rich protein-like protein (SH3BGRL), a downstream effector of PRL-3, plays a tumor suppressive role in solid tumors, but it remains elusive in AML. Here, we followed up and validated the relevance of SH3BGRL expression to AML progression in 116 cases. Results showed that SH3BGRL is down-regulated in 62.37% AML cases with poor prognosis. Cases with positive response to therapy accompanies with SH3GRL expression restoration. Mechanistically, SH3BGRL down-regulation promotes AML cell cycle progression and enhances the anti-apoptotic ability to drug cytotoxicity. While ectopic SH3BGRL blocks AML cell cycle and proliferation to sensitize them to therapeutic drugs via apoptosis. Xenograft assays further confirmed the suppressive role of SH3BGRL in leukemogenesis. Thus, our results demonstrated that SH3BGRL is a novel crucial player in AML progression and could be both a potential diagnostic and prognostic marker.
引用
收藏
页码:918 / 930
页数:13
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