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

Objective To explore correlation of seven apoptosis-related proteins （Hsp9Oa, 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 Hsp90a-, 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.