Increased expression of amyloid precursor protein promotes proliferation and migration of AML1/ETO-positive leukemia cells and can be inhibited by panobinostat
Increased expression of amyloid precursor protein promotes proliferation and migration of AML1/ETO-positive leukemia cells and can be inhibited by panobinostat
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淀粉样前体蛋白表达增加可促进 AML1/ETO 阳性白血病细胞的增殖和迁移，并被帕比司他抑制。
DOI：
10.4149/neo_2015_105
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发表时间：
2015-01-01
期刊：
影响因子：
3
通讯作者：
Meng, F. Y.
中科院分区：
文献类型：
--
作者：
Wang, C. L.;Ding, B. J.;Meng, F. Y.
淀粉样前体蛋白（APP）是一种高度保守的整合膜蛋白，广泛表达于各种类型的细胞中。此前我们发现 AML1/ETO 阳性急性髓系白血病 (AML) 患者中 APP 过度表达与髓外浸润发生率较高相关，提示预后不良。在本研究中，我们试图确定 APP 在 AML1/ETO 阳性白血病细胞中的作用。 Western blotting 和 qRT-PCR 分析表明，t (8; 21)/AML1/ETO 阳性 M2 型 AML 细胞系 Kasumi-1 中 APP 的蛋白水平显着较高。基于慢病毒的 RNA 干扰 (RNAi) 稳定敲低 APP 会显着损害 Kasumi-1 细胞的集落形成和迁移能力，而敲低 APP 对细胞活力、细胞凋亡、细胞周期和分化影响很小。我们进一步探讨了泛组蛋白脱乙酰酶抑制剂帕比司他是否可以降低 Kasumi-1 细胞中 APP 的蛋白水平。帕比司他治疗导致 Kasumi-1 细胞中 APP 耗尽。这些发现表明APP的过度表达参与促进AML1/ETO阳性白血病细胞的增殖和迁移，并且可以被帕比司他抑制，这为AML1/ETO阳性AML的治疗提供了诱人的前景。
Amyloid precursor protein (APP) is a highly conserved integral membrane protein extensively expressed in various types of cells. Previously we found that overexpression of APP in patients with AML1/ETO-positive acute myeloid leukemia (AML) associated with a higher incidence of extramedullary infiltrationin and indicate a poor prognosis. In this study, we attempted to define the roles of APP in AML1/ETO-positive leukemia cells. Western blotting and qRT-PCR analysis showed that protein levels of APP are significantly higher in Kasumi-1, a t (8; 21)/AML1/ETO-positive M2-type AML cell line. Stable knockdown of APP by lentivirus-based RNA interference (RNAi) dramatically impaired colony-formation and migration ability of Kasumi-1 cells, whereas APP knockdown had very little effect on cell viability, apoptosis, cell cycle and differentiation. We further explored whether the pan-histone deacetylase inhibitor panobinostat could deplete the protein levels of APP in Kasumi-1 cells. Treatment with panobinostat caused depletion of APP in Kasumi-1 cells. These findings indicate that overexpression of APP is involved in promoting proliferation and migration of AML1/ETO-positive leukemia cells and can be inhibited by panobinostat, which provide an attractive prospect for treatment of AML1/ETO-positive AML.