LI Hui Ling; HUANG Xue Ping; ZHOU Xin Hua; JI Tian Hai; WU Zi Qing; WANG Zhi Qiang; JIANG Hui Yong; LIU Fan Rong; ZHAO Tong

doi:10.3967/0895-3988.2011.06.007

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

LI Hui Ling, HUANG Xue Ping, ZHOU Xin Hua, JI Tian Hai, WU Zi Qing, WANG Zhi Qiang, JIANG Hui Yong, LIU Fan Rong, ZHAO Tong

文章导航 > Biomedical and Environmental Sciences > 2011 > 24(6): 630-641

LI Hui Ling, HUANG Xue Ping, ZHOU Xin Hua, JI Tian Hai, WU Zi Qing, WANG Zhi Qiang, JIANG Hui Yong, LIU Fan Rong, ZHAO Tong. 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[J]. Biomedical and Environmental Sciences, 2011, 24(6): 630-641. doi: 10.3967/0895-3988.2011.06.007

Citation:

LI Hui Ling, HUANG Xue Ping, ZHOU Xin Hua, JI Tian Hai, WU Zi Qing, WANG Zhi Qiang, JIANG Hui Yong, LIU Fan Rong, ZHAO Tong. 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[J]. Biomedical and Environmental Sciences, 2011, 24(6): 630-641. doi: 10.3967/0895-3988.2011.06.007

doi: 10.3967/0895-3988.2011.06.007

基金项目: the National Natural Science Foundation of China(30901169)

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

Department of Pathology, Nanfang Hospital affiliated to Southern Medical University, Guangzhou 510515 Gruangdong, China
Department of Pathology, Nanfang Hospital affiliated to Southern Medical University, Guangzhou 510515 Gruangdong, China;Department of Pathology, School of Basic Medical Science, Southern Medical University,Guangzho 510515, Guangdong, China
Department of Pathology, School of Basic Medical Science, Southern Medical University,Guangzho 510515, Guangdong, China

Funds: the National Natural Science Foundation of China(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.
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Abstract: 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.
- ALK+ALCL /
- NPM-ALK /
- Prognostic factors /
- Apoptosis /
- Herbimycin A

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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

doi: 10.3967/0895-3988.2011.06.007

基金项目: the National Natural Science Foundation of China(30901169)

刊出日期: 2011-12-20

关键词:

ALK+ALCL /

NPM-ALK /

Prognostic factors /

Apoptosis /

Herbimycin A

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.

English Abstract

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

Department of Pathology, Nanfang Hospital affiliated to Southern Medical University, Guangzhou 510515 Gruangdong, China

Department of Pathology, Nanfang Hospital affiliated to Southern Medical University, Guangzhou 510515 Gruangdong, China;Department of Pathology, School of Basic Medical Science, Southern Medical University,Guangzho 510515, Guangdong, China

Department of Pathology, School of Basic Medical Science, Southern Medical University,Guangzho 510515, Guangdong, China

Funds: the National Natural Science Foundation of China(30901169)

Publish Date: 2011-12-20

Keywords:

Abstract: 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.

Citation:

LI Hui Ling, HUANG Xue Ping, ZHOU Xin Hua, JI Tian Hai, WU Zi Qing, WANG Zhi Qiang, JIANG Hui Yong, LIU Fan Rong, ZHAO Tong. 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[J]. Biomedical and Environmental Sciences, 2011, 24(6): 630-641. doi: 10.3967/0895-3988.2011.06.007