Wang Youxin, Chang Naibai, Zhang Tian, Liu Hui, Ma Wenzhan, Chu Qiaoyun, Lai Qingxuan, Liu Lixin, Wang Wei
College of Life Science, Graduate University of Chinese Academy of Sciences, Beijing, China.
Genet Test Mol Biomarkers. 2010 Feb;14(1):127-33. doi: 10.1089/gtmb.2009.0145.
We earlier identified a novel gene human CAP10-like protein 46 KD (hCLP46) from human acute myelogenous leukemia (AML) transformed from myelodysplastic syndrome CD34(+) cells, but the function of this gene remains unclear. In this study, a real-time polymerase chain reaction-based assay was developed to quantify expression of hCLP46 in the peripheral blood of AML and T-acute lymphoblastic leukemia (T-ALL) primary samples and in six leukemic cell lines. Also, we investigated expression of CDKN2A/B and the apoptosis in U937 cells when hCLP46 is downregulated in vitro.
Our findings showed that hCLP46 was overexpressed in AML, T-ALL, and the leukemic cell lines. Suppressing hCLP46 overexpression had no effect on expression of CDKN2A/B and apoptosis of U937 cells.
Considering that hCLP46 has the capability of modifying the Notch pathway, our finding adds weight to the importance of Notch signaling in hematopoiesis and suggests that overexpression of hCLP46 might be an early event in the pathogenesis of AML and T-ALL.
我们之前从骨髓增生异常综合征CD34(+)细胞转化而来的人类急性髓性白血病（AML）中鉴定出一种新基因——人类CAP10样蛋白46KD（hCLP46），但该基因的功能仍不清楚。在本研究中，我们开发了一种基于实时聚合酶链反应的检测方法，用于定量hCLP46在AML和T急性淋巴细胞白血病（T-ALL）原代样本外周血以及六种白血病细胞系中的表达。此外，我们还研究了体外下调hCLP46时U937细胞中CDKN2A/B的表达及细胞凋亡情况。
我们的研究结果表明，hCLP46在AML、T-ALL及白血病细胞系中过表达。抑制hCLP46的过表达对U937细胞中CDKN2A/B的表达及细胞凋亡没有影响。
鉴于hCLP46具有调节Notch信号通路的能力，我们的研究结果进一步强调了Notch信号在造血过程中的重要性，并表明hCLP46的过表达可能是AML和T-ALL发病机制中的早期事件。
