López Villar Elena, Wang Xiangdong, Madero Luis, Cho William C
Department of Oncohematology and Pediatrics, Hospital Infantil Universitario Niño Jesús, Universidad Autónoma de Madrid, Madrid, Spain.
J Cell Mol Med. 2015 Jan;19(1):46-52. doi: 10.1111/jcmm.12507. Epub 2014 Dec 23.
Oncoproteomics is an important innovation in the early diagnosis, management and development of personalized treatment of acute lymphoblastic leukaemia (ALL). As inherent factors are not completely known - e.g. age or family history, radiation exposure, benzene chemical exposure, certain viral exposures such as infection with the human T-cell lymphoma/leukaemia virus-1, as well as some inherited syndromes may raise the risk of ALL - each ALL patient may modify the susceptibility of therapy. Indeed, we consider these unknown inherent factors could be explained via coupling cytogenetics plus proteomics, especially when proteins are the ones which play function within cells. Innovative proteomics to ALL therapy may help to understand the mechanism of drug resistance and toxicities, which in turn will provide some leads to improve ALL management. Most important of these are shotgun proteomic strategies to unravel ALL aberrant signalling networks. Some shotgun proteomic innovations and bioinformatic tools for ALL therapies will be discussed. As network proteins are distinctive characteristics for ALL patients, unrevealed by cytogenetics, those network proteins are currently an important source of novel therapeutic targets that emerge from shotgun proteomics. Indeed, ALL evolution can be studied for each individual patient via oncoproteomics.
肿瘤蛋白质组学是急性淋巴细胞白血病(ALL)早期诊断、治疗管理以及个性化治疗发展方面的一项重要创新。由于一些内在因素尚未完全明确,例如年龄、家族病史、辐射暴露、苯化学物质暴露、某些病毒暴露(如感染人类T细胞淋巴瘤/白血病病毒-1)以及一些遗传综合征可能会增加患ALL的风险,所以每位ALL患者对治疗的敏感性可能会有所不同。实际上,我们认为这些未知的内在因素可以通过结合细胞遗传学和蛋白质组学来解释,尤其是当蛋白质在细胞内发挥功能时。ALL治疗中的创新蛋白质组学有助于理解耐药性和毒性机制,进而为改善ALL治疗管理提供一些线索。其中最重要的是鸟枪法蛋白质组学策略,用于揭示ALL异常信号网络。本文将讨论一些ALL治疗中的鸟枪法蛋白质组学创新和生物信息学工具。由于网络蛋白是ALL患者的独特特征,细胞遗传学无法揭示这些特征,因此这些网络蛋白目前是鸟枪法蛋白质组学产生的新型治疗靶点的重要来源。事实上,可以通过肿瘤蛋白质组学对每位ALL患者的病情进展进行研究。