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.