Kohnke Philippa L, Mulligan Stephen P, Christopherson Richard I
University of Sydney, School of Molecular and Microbial Biosciences, Maze Crescent, Sydney, New South Wales 2006, Australia.
Curr Opin Mol Ther. 2009 Dec;11(6):603-10.
Knowledge of protein expression in the plasma membrane of leukemia cells has contributed to improvements in the detection and treatment of hematological malignancies. Recently engineered antibodies against leukemia surface molecules have improved therapeutic efficacy compared with earlier agents, but there are still side effects. An increased understanding of the surface expression profiles and interactions of membrane proteins on leukemia cells will facilitate the expansion of the role of antibodies in therapy and enable the identification of novel biomarkers for the various stages of leukemogenesis and leukemia progression. Proteomic analysis enables the identification of thousands of proteins in a membrane extract and provides information on their relative abundance, interactions and post-translational modifications. Plasma membrane proteome analysis of leukemia cells can be used to define biomarkers for diagnosis, classification, prognosis and progression monitoring, as well as to predict therapeutic response or resistance. The effects of chemotherapy on the surface proteome and the functional consequences of perturbations to membrane protein networks can provide insights into leukemia cell signaling and survival mechanisms. Surface proteins that are differentially expressed on leukemia cells are prospective targets for the development of engineered antibodies or small-molecule therapeutics. This review focuses on recent discoveries in leukemia membrane proteomics and the potential for future research into leukemia classification and drug target identification.
白血病细胞质膜中蛋白质表达的相关知识推动了血液系统恶性肿瘤检测与治疗的进展。与早期药物相比，近期研发的针对白血病表面分子的抗体提高了治疗效果，但仍存在副作用。深入了解白血病细胞膜蛋白的表面表达谱及其相互作用，将有助于扩大抗体在治疗中的作用，并能识别白血病发生和进展各阶段的新型生物标志物。蛋白质组学分析能够鉴定膜提取物中的数千种蛋白质，并提供有关它们相对丰度、相互作用和翻译后修饰的信息。白血病细胞质膜蛋白质组分析可用于确定诊断、分类、预后和病情进展监测的生物标志物，还能预测治疗反应或耐药性。化疗对表面蛋白质组的影响以及膜蛋白网络扰动的功能后果，可为白血病细胞信号传导和存活机制提供见解。白血病细胞上差异表达的表面蛋白是研发工程抗体或小分子疗法的潜在靶点。本综述聚焦于白血病膜蛋白质组学的最新发现以及未来白血病分类和药物靶点识别研究的潜力。
