The AKT kinase is activated in multiple myeloma tumor cells
The AKT kinase is activated in multiple myeloma tumor cells
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DOI：
10.1182/blood.v98.9.2853
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发表时间：
2001-11-01
期刊：
影响因子：
20.3
通讯作者：
Lichtenstein, A
中科院分区：
文献类型：
--
作者：
Hsu, JH;Shi, YJ;Lichtenstein, A
用磷酸特异性抗AKT抗体对存档骨髓进行免疫组织化学(IHC)检测。26例多发性骨髓瘤(MM)患者骨髓活检标本的免疫组化染色显示，恶性浆细胞呈细胞膜特异性的磷酸化AKT染色，而非恶性造血细胞未见染色。抗体被磷酸化的AKT多肽预吸收，而不是非磷酸化的多肽，取消染色。I期或阴燃MM患者骨髓浆细胞染色频率明显低于III期MM患者。10例临床意义不明的单克隆性丙种球蛋白病患者的浆细胞未见抗体染色。为了探讨AKT激活的意义，我们还研究了2个从原代MM细胞培养开始的细胞系。两者均表现为AKT的结构性激活。阻断AKT的激活和活性，通过暴露于Wortmannin或通过异位表达显性负AKT突变体，导致MM细胞在体外的生长受到抑制。这些结果表明AKT激酶的激活是多发性骨髓瘤细胞的特征，提示AKT活性对多发性骨髓瘤细胞的增殖很重要。(C)2001年，由美国血液病学会提供。
Immunohistochemistry (IHC) was performed on archived bone marrow (BM) with a phosphospecific anti-AKT antibody. IHC on 26 BM biopsies from patients with multiple myeloma (MM) demonstrated phospho-AKT staining of malignant plasma cells in a cell membrane-specific pattern, whereas nonmalignant hematopoietic cells did not stain. Preabsorption of the antibody with phosphorylated AKT peptide, but not nonphosphorylated peptide, abrogated staining. Frequency of plasma cell staining in BMs of patients with stage I or smoldering MM was significantly less than that of stage III MM marrows. Plasma cells in 10 patients with monoclonal gammopathy of undetermined significance were not stained by the antibody. To investigate the significance of AKT activation, 2 cell lines initiated from cultures of primary MM cells were also studied. Both demonstrated constitutive AKT activation. Interruption of AKT activation and activity, achieved by either exposure to wortmannin or by ectopic expression of a dominant negative AKT mutant, resulted in inhibition of MM cell growth in vitro. These results indicate that activation of the AKT kinase is a characteristic of MM cells and suggest that AKT activity is important for MM cell expansion. (C) 2001 by The American Society of Hematology.