Correlation of seven biological factors (Hsp90a, p53, MDM2, Bcl-2, Bax, Cytochrome C, and Cleaved caspase3) with clinical outcomes of ALK+ anaplastic large-cell lymphoma.
- Author:
Hui Ling LI
1
;
Xue Ping HUANG
;
Xin Hua ZHOU
;
Tian Hai JI
;
Zi Qing WU
;
Zhi Qiang WANG
;
Hui Yong JIANG
;
Fan Rong LIU
;
Tong ZHAO
Author Information
- Publication Type:Journal Article
- MeSH: Adolescent; Adult; Aged; Apoptosis; drug effects; Apoptosis Regulatory Proteins; metabolism; Benzoquinones; pharmacology; Biomarkers, Tumor; metabolism; Blotting, Western; Cell Culture Techniques; Cell Survival; drug effects; Child; Child, Preschool; Disease-Free Survival; Enzyme Inhibitors; pharmacology; Female; Flow Cytometry; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Lactams, Macrocyclic; pharmacology; Lymphoma, Large-Cell, Anaplastic; enzymology; metabolism; pathology; Male; Microscopy, Fluorescence; Middle Aged; Neoplasm Staging; Prognosis; Protein-Tyrosine Kinases; metabolism; Receptor Protein-Tyrosine Kinases; antagonists & inhibitors; metabolism; Retrospective Studies; Rifabutin; analogs & derivatives; Young Adult
- From: Biomedical and Environmental Sciences 2011;24(6):630-641
- CountryChina
- Language:English
-
Abstract:
OBJECTIVETo explore correlation of seven apoptosis-related proteins (Hsp90a, p53, MDM2, Bcl-2, Bax, Cytochrome C, and Cleaved caspase3) with clinical outcomes of ALK+ anaplastic large-cell lymphoma (ALCL).
METHODSUsing 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.
RESULTSThe 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.
CONCLUSIONOur 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.
