BMP7 Expression Correlates with Secondary Drug Resistance in Mantle Cell Lymphoma

Valérie Camara-Clayette (1, 2) , Serge Koscielny (3) , Sébastien Roux (1, 2) , Thierry Lamy (4) , Jacques Bosq (5) , Marc Bernard (6) , Thierry Fest (6, 4) , Vladimir Lazar (1) , Gilbert Lenoir (1) , Vincent Ribrag (2, 7)

1 Institut de Recherche Intégrée en cancérologie à Villejuif (IRCIV)
2 Hématopoïèse normale et pathologique
3 SBE - Service de biostatistique et d'épidémiologie
4 MiCa - Microenvironnement et cancer
5 Département de biologie et pathologie médicales [Gustave Roussy]
6 Service d'hématologie clinique
7 Département de médecine oncologique [Gustave Roussy]

Purpose We designed a gene profiling experiment to identify genes involved in secondary drug resistance in mantle cell lymphomas (MCL). Experimental Design We obtained paired tissue samples collected from the same patients before treatment and after relapse or progression. Variations in gene expression between the 2 samples were estimated for 5 patients. For each gene, the mean variation was estimated for patients with a refractory primary tumor and for responders who developed secondary drug resistance. Nine genes of interest were selected on the basis of the magnitude and statistical significance of the variation of expression in responders and non-responders. Results BMP7 was the only one with significantly increased expression at relapse in patients who developed secondary resistance. Validation of BMP7 as a key gene involved in secondary resistance was performed using cultures of cell line. Incubation of BMP7 with MCL cell lines increased their resistance to bortezomib and cytarabine, while inhibition of BMP7 expression by siRNA correlated with increased cell death linked to drug application. Conclusion Variations in gene expression after treatment point out BMP7 as a key gene involved in secondary resistance in mantle cell lymphoma.

Domains: Life Sciences [q-bio]; Cancer

Valérie Camara-Clayette, Serge Koscielny, Sébastien Roux, Thierry Lamy, Jacques Bosq, et al.. BMP7 Expression Correlates with Secondary Drug Resistance in Mantle Cell Lymphoma. PLoS ONE, 2013, 8 (9), pp.e73993. ⟨10.1371/journal.pone.0073993⟩. ⟨hal-00935237⟩