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

SH3BGRL as a novel prognostic biomarker is down-regulated in acute myeloid leukemia
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SH3BGRL 作为一种新型预后生物标志物在急性髓系白血病中下调

DOI:
10.1080/10428194.2017.1344843
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发表时间:
2018-04
影响因子:
2.6
通讯作者:
王海河
王海河
中科院分区:
医学4区
文献类型:
--
作者:
Limei Xu;Mingming Zhang;Hui Li;Wen Guan;Bin Liu;Fengqi Liu;Shulan Yang;Xiuzheng Tong;王海河

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摘要PRL-3的表达与急性髓细胞白血病(AML)的进展和耐药呈正相关。SH 3-domain-binding glutamic acid-rich protein-like protein(SH 3BGRL)是PRL-3的下游效应子,在实体瘤中发挥肿瘤抑制作用,但在AML中仍然难以找到。在此,我们随访并验证了116例AML患者中SH 3BGRL表达与AML进展的相关性。结果表明,62.37%的AML患者SH 3BGRL表达下调,预后不良。对治疗有阳性反应的病例伴随着SH 3GRL表达的恢复。机制上,SH 3BGRL下调促进AML细胞周期进展并增强对药物细胞毒性的抗凋亡能力。而异位的SH 3BGRL通过凋亡阻断AML细胞周期和增殖,使其对治疗药物敏感。异种移植物测定进一步证实了SH 3BGRL在白血病发生中的抑制作用。因此,我们的研究结果表明,SH 3BGRL是AML进展中的一个新的关键参与者,并且可能是一个潜在的诊断和预后标志物。
Abstract 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.
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