Abstract
Accumulating evidence suggests that lack of balance between proliferation and apoptosis may lead to clonal expansion and cancer emergence. In diffuse large B cell lymphoma (DLBCL), survivin expression by tumor cells has been recently described as a poor prognostic marker. We assessed the relationship between survivin gene up-regulation and several other factors involved in either cell cycle or apoptosis control. The expression of 34 genes from 27 cases of DLBCL with typical IPI factor-related poor prognostic outcome was analyzed by RNase protection assay. Using non-neoplastic tissues and low grade lymphomas as control, survivin expression was high in 80% of the cases without significant relation to patient overall survival (P = 0.64). However, the expression of several genes encoding for cell cycle inhibitors, cyclins, Bcl-2 or IAP family factors was significantly associated with the survivin up-regulation. Gene expression profiling showed that both survivin and cyclin B expression can define two subgroups of DLBCL: the previously described germinal center-like and activated B-like lymphomas, determined by protein expression analysis. We also identified a preferential survivin–cyclin B relationship (P = 0.017), suggesting that cyclin B over-expression, when linked to survivin over-expression in aggressive forms of lymphoma, might demonstrate a specific G2/M transition promotion.
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Acknowledgements
This work was supported by the Ligue Contre le Cancer du Doubs and AMGEN SA Company, Neuilly, France. We wish to thank Dr Frédéric Mauny (Département d'Information Médicale, Besançon) for providing his expertise in the statistical analysis.
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Kuttler, F., Valnet-Rabier, MB., Angonin, R. et al. Relationship between expression of genes involved in cell cycle control and apoptosis in diffuse large B cell lymphoma: a preferential survivin–cyclin B link. Leukemia 16, 726–735 (2002). https://doi.org/10.1038/sj.leu.2402427
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DOI: https://doi.org/10.1038/sj.leu.2402427
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