Department of Clinical and Experimental Medicine, Hematology and Clinical Immunology Branch, University of Padua School of Medicine, Padua, Italy.
Leukemia. 2012 Jun;26(6):1174-9. doi: 10.1038/leu.2011.385. Epub 2012 Jan 13.
CK2 is a multitask kinase whose role is essential for a countless number of cellular processes, many of which are critical for blood cell development. A prevailing task for this kinase rests on counteracting programmed cell death triggered by multiple stimuli. CK2 is overexpressed in many solid tumors and in vivo mouse models have proven its tumorigenic potential. Recent data have suggested that CK2 may also have a significant role in the pathogenesis of hematopoietic tumors, such as multiple myeloma, chronic lymphocytic leukemia, acute myelogenous leukemia, acute lymphoblastic leukemia and chronic myeloproliferative neoplasms. CK2 regulates hematopoiesis-associated signaling pathways and seems to reinforce biochemical cascades indispensable for tumor growth, proliferation and resistance to conventional and novel cytotoxic agents. Although its activity is multifold, recent evidence supports the rationale of CK2 inhibition as a therapeutic strategy in solid and hematological tumors and phase-I clinical trials are in progress to test the efficacy of this innovative therapeutic approach. In this review, we will summarize the data supporting CK2 as an oncogenic kinase in blood tumors and we will describe some critical signaling pathways, whose regulation by this protein kinase may be implicated in tumorigenesis.
CK2 是一种多功能激酶，其作用对无数细胞过程至关重要，其中许多过程对血细胞发育至关重要。该激酶的一个主要任务是对抗多种刺激引发的程序性细胞死亡。CK2 在许多实体瘤中过度表达，体内小鼠模型已证明其具有致瘤潜力。最近的数据表明，CK2 也可能在造血肿瘤的发病机制中发挥重要作用，如多发性骨髓瘤、慢性淋巴细胞白血病、急性髓系白血病、急性淋巴细胞白血病和慢性骨髓增生性肿瘤。CK2 调节与造血相关的信号通路，并似乎加强了肿瘤生长、增殖和对传统及新型细胞毒药物耐药性所必需的生化级联反应。尽管其活性多种多样，但最近的证据支持 CK2 抑制作为实体瘤和血液系统肿瘤的治疗策略的合理性，正在进行 I 期临床试验以测试这种创新治疗方法的疗效。在这篇综述中，我们将总结支持 CK2 作为血液肿瘤致癌激酶的证据，并描述一些关键的信号通路，其可能涉及蛋白激酶的调节与肿瘤发生。
