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Correlation of Seven Biological Factors(Hsp90α,p53,MDM2,Bcl-2,Bax,Cytochrome C,and Cleaved caspase3)with Clinical Outcomes of ALK+ Anaplastic Large-cell Lymphoma

查看全文 作　　者：LI Hui [1]Ling;HUANG Xue [1,2]Ping;ZHOU Xin [2]Hua;JI Tian [2]Hai;WU Zi [2]Qing;WANG Zhi [1]Qiang;JIANG Hui [1]Yong;LIU Fan [2]Rong;ZHAO [1,2]Tong 高影响力作者 机构地区：[1]Department of Pathology, Nanfang Hospital affiliated to Southern Medical University, Guangzhou 510515 Guangdong, China;[2]Department of Pathology, School of Basic Medical Science, Southern Medical University, Guangzho 510515, Guangdong, China高影响力机构 出　　处：《Biomedical and Environmental Sciences》索引2011年第24卷第6期,共12页高影响力期刊 基　　金：supported by the National Natural Science Foundation of China(No.30901169) 摘　　要：Objective To explore correlation of seven apoptosis‐related proteins (Hsp90α,p53,MDM2,Bcl‐2,Bax,Cytochrome C,and Cleaved caspase3) with clinical outcomes of ALK+ anaplastic large‐cell lymphoma (ALCL).Methods Using immunohistochemistry and immunofluorescence double staining methods,the expressions of these seven apoptosis‐associated proteins were studied to clarify their relationship with clinical outcomes of 36 ALK+ and 25 ALK‐ systemic ALCL patients enrolled between 1996 and 2006.The relationship of these apoptosis‐regulating proteins with NPM‐ALK status was also evaluated with the tyrosine inhibitor herbimycin A (HA) in vitro by immunocytochemistry,Western blotting and flow cytometric assays.Results The presence of Hsp90α‐,MDM2‐,Bax‐,Cytochrome C,and Cleaved caspase3‐positive tumor cells was found significantly different in ALK+ and ALK‐ ALCLs ,which was correlated with highly favorable clinical outcome.The Bcl‐2‐ and p53‐positive tumor cells were found in groups of patients with unfavorable prognosis.Inhibition of NPM‐ALK by HA could reactivate the p53 protein and subsequent apoptosis‐related proteins and therefore induced apoptosis in ALK+ ALCL cells.Conclusion Our results suggest that these seven proteins might be involved in apoptosis regulation and associated with clinical outcome of ALK+ systemic ALCLs.We also reveal a dynamic chain relation that NPM‐ALK regulates p53 expression and subsequent apoptosis cascade in ALK+ ALCLs. 关 键 词：BAX蛋白 细胞色素C BCL-2 P53蛋白 临床疗效 MDM2 ALK 淋巴瘤
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