LAMP4在急性髓系白血病中的表达与功能分析

Expression and function analysis of LAMP4 in acute myeloid leukemia

急性髓系白血病(acute myeloid leukemia,AML)是一种侵袭性的造血恶性肿瘤,深入了解AML发生发展的分子机制对于开发新的治疗方法是必要的。LAMP4为溶酶体相关膜蛋白家族成员,在肿瘤病情进展中的作用因癌症类型而异。该研究发现LAMP4在AML中特异性高表达,并可作为该病的潜在分子诊断标志物。细胞功能研究发现敲低LAMP4能够显著促进AML细胞凋亡和细胞分化。细胞亚细胞定位发现,LAMP4主要定位于溶酶体上,并且在佛波酯(Phorbol 12-myristate 13-acetate,PMA)的诱导下,LAMP4能够从溶酶体上脱落下来,初步证明LAMP4抑制细胞分化的癌性功能与溶酶体定位相关。研究表明LAMP4可为AML潜在的临床诊断分子标记物,是一个AML治疗的潜在靶点。

Acute myeloid leukemia(AML)is a kind of aggressive hematopoietic malignancies.Understanding the molecular mechanism of AML generation and progression is necessary to develop novel therapies for the disease.LAMP4 is a member of the lysosomal related membrane protein family,and its diverse roles in tumor progression have been reported different in certain cancers.In this study,we found that LAMP4 expressed a high level in AML patient samples compared with those controls,suggesting its potential as a biomarker for AML.Functional studies showed that knocking down LAMP4 can significantly promote the cell apoptosis and differentiation of AML cells.Furthermore,LAMP4 was found to locate at lysosome,and it can be dropped from the lysosome under the Phorbol 12-myristate 13-acetate(PMA)treatment,indicating that the function of LAMP4 suppressing the cell differentiation was related to its lysosomal localization.The study suggested that LAMP4 could be served as a potential biomarker and target for AML.