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 / 生物医学与环境科学(英文)
Biomedical and Environmental Sciences
; (12): 630-641, 2011.
Article
in En
| WPRIM
| ID: wpr-235588
Responsible library:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To 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).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>
Full text:
1
Index:
WPRIM
Main subject:
Pathology
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Pharmacology
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Prognosis
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Protein-Tyrosine Kinases
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Immunohistochemistry
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Biomarkers, Tumor
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Cell Survival
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Blotting, Western
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Retrospective Studies
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Benzoquinones
Type of study:
Observational_studies
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Prognostic_studies
Limits:
Adolescent
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Adult
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Aged
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Child
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Child, preschool
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Female
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Humans
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Male
Language:
En
Journal:
Biomedical and Environmental Sciences
Year:
2011
Type:
Article