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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.
Objective To explore the 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 of 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 foun d in groups with 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. Confluence 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.