Xu Limei, Zhang Mingming, Li Hui, Guan Wen, Liu Bin, Liu Fengqi, Wang Hehua, Li Juan, Yang Shulan, Tong Xiuzhen, Wang Haihe
a Department of Hematology , The First Affiliated Hospital, Sun Yat-sen University , Guangzhou , China.
b Department of Biochemistry, Zhongshan School of Medicine , Sun Yat-sen University , Guangzhou , China.
Leuk Lymphoma. 2018 Apr;59(4):918-930. doi: 10.1080/10428194.2017.1344843. Epub 2017 Jul 6.
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.
磷酸酶PRL-3的表达与急性髓系白血病（AML）的进展和耐药性呈正相关。富含谷氨酸的SH3结构域结合蛋白样蛋白（SH3BGRL）是PRL-3的下游效应物，在实体瘤中发挥肿瘤抑制作用，但在AML中的作用尚不清楚。在此，我们对116例患者进行随访并验证了SH3BGRL表达与AML进展的相关性。结果显示，在预后不良的62.37%的AML病例中SH3BGRL表达下调。对治疗有阳性反应的病例伴有SH3GRL表达恢复。机制上，SH3BGRL下调促进AML细胞周期进程并增强对药物细胞毒性的抗凋亡能力。而异位表达的SH3BGRL可阻断AML细胞周期和增殖，通过凋亡使它们对治疗药物敏感。异种移植试验进一步证实了SH3BGRL在白血病发生中的抑制作用。因此，我们的结果表明SH3BGRL是AML进展中的一个新的关键因子，并且可能是一个潜在的诊断和预后标志物。
