Max-Planck-Institute of Experimental Medicine, Hermann-Rein-Str, 3, 37075 Göttingen, Germany.
Mol Cancer. 2010 Jan 27;9:18. doi: 10.1186/1476-4598-9-18.
The voltage-gated potassium channel hEag1 (KV10.1) has been related to cancer biology. The physiological expression of the human channel is restricted to the brain but it is frequently and abundantly expressed in many solid tumors, thereby making it a promising target for a specific diagnosis and therapy. Because chronic lymphatic leukemia has been described not to express hEag1, it has been assumed that the channel is not expressed in hematopoietic neoplasms in general.
Here we show that this assumption is not correct, because the channel is up-regulated in myelodysplastic syndromes, chronic myeloid leukemia and almost half of the tested acute myeloid leukemias in a subtype-dependent fashion. Most interestingly, channel expression strongly correlated with increasing age, higher relapse rates and a significantly shorter overall survival. Multivariate Cox regression analysis revealed hEag1 expression levels in AML as an independent predictive factor for reduced disease-free and overall survival; such an association had not been reported before. As a functional correlate, specific hEag1 blockade inhibited the proliferation and migration of several AML cell lines and primary cultured AML cells in vitro.
Our observations implicate hEag1 as novel target for diagnostic, prognostic and/or therapeutic approaches in AML.
电压门控钾通道 hEag1（KV10.1）与癌症生物学有关。该人类通道的生理表达仅限于大脑，但在许多实体瘤中频繁且大量表达，因此成为特异性诊断和治疗的有希望的靶标。由于慢性淋巴细胞白血病被描述为不表达 hEag1，因此人们假设该通道一般不在造血性肿瘤中表达。
在这里，我们表明这种假设是不正确的，因为通道在骨髓增生异常综合征、慢性髓性白血病中上调，并且在几乎一半的测试急性髓性白血病中以亚型依赖的方式上调。最有趣的是，通道表达与年龄增加、更高的复发率和显著更短的总生存期强烈相关。多变量 Cox 回归分析显示 AML 中的 hEag1 表达水平是降低无病生存期和总生存期的独立预测因子；以前没有报道过这种关联。作为功能相关，特异性 hEag1 阻断在体外抑制了几种 AML 细胞系和原代培养的 AML 细胞的增殖和迁移。
我们的观察结果表明 hEag1 是 AML 中用于诊断、预后和/或治疗方法的新靶标。
