Ersvaer Elisabeth, Zhang Jian-Ying, McCormack Emmet, Olsnes Astrid, Anensen Nina, Tan Eng M, Gjertsen Bjørn Tore, Bruserud Oystein
Institute of Medicine, University of Bergen, Bergen, Norway.
Eur J Haematol. 2007 Sep;79(3):210-25. doi: 10.1111/j.1600-0609.2007.00899.x. Epub 2007 Jul 26.
Aberrant expression of cyclin B1, a cell cycle regulator, is related to prognosis in various human malignancies. Additionally, cytoplasmic expression of cyclin B1 in epithelial malignancies is associated with a specific T-cell response and presumably also a humoral immune response. We therefore investigated (i) whether a similar expression pattern could be detected in native human acute myelogenous leukemia (AML) cells and (ii) whether cyclin B1 specific antibodies could be detected in AML.
AML cell expression of cyclin B1 was analyzed by flow cytometry and confocal microscopy. Humoral immune response in AML patient sera against cyclin B1 was analyzed by ELISA.
AML cell expression of cyclin B1 was detected for all 42 patients; but the percentage of cyclin B1 positive cells showed a wide variation between patients. Confocal microscopy demonstrated that 32/42 (76%) patient samples showed abnormal cytoplasmic expression. Furthermore, the cytoplasmic expression was maintained after 14 d of in vitro culture and differentiation of the AML cells towards a dendritic cell phenotype. Cyclin B1 specific serum antibodies could be detected for seven of 65 patients with untreated AML.
Our studies demonstrate that primary human AML cells show aberrant cytoplasmic expression of cyclin B1 for a majority of patients and a specific humoral immune response was also detected for a subset of patients with untreated leukemia.
细胞周期调节因子细胞周期蛋白B1(cyclin B1)的异常表达与多种人类恶性肿瘤的预后相关。此外,上皮性恶性肿瘤中cyclin B1的细胞质表达与特定的T细胞反应相关,可能也与体液免疫反应相关。因此,我们研究了(i)在天然人类急性髓系白血病(AML)细胞中是否能检测到类似的表达模式,以及(ii)在AML中是否能检测到cyclin B1特异性抗体。
通过流式细胞术和共聚焦显微镜分析AML细胞中cyclin B1的表达。采用酶联免疫吸附测定(ELISA)分析AML患者血清中针对cyclin B1的体液免疫反应。
42例患者的AML细胞均检测到cyclin B1表达;但cyclin B1阳性细胞百分比在患者之间存在很大差异。共聚焦显微镜显示,32/42(76%)例患者样本呈现异常细胞质表达。此外,AML细胞在体外培养14天并向树突状细胞表型分化后,细胞质表达得以维持。65例未经治疗的AML患者中有7例可检测到cyclin B1特异性血清抗体。
我们的研究表明,大多数原发性人类AML细胞显示cyclin B1异常细胞质表达,并且在一部分未经治疗的白血病患者中也检测到了特异性体液免疫反应。