SOX11 regulates PAX5 expression and blocks terminal B-cell differentiation in aggressive mantle cell lymphoma

Maria Carmela Vegliante, Jara Palomero, Patricia Pérez-Galán, Gaël Roué, Giancarlo Castellano, Alba Navarro, Guillem Clot, Alexandra Moros, Helena Suárez-Cisneros, Sílvia Beà, Luis Hernández, Anna Enjuanes, Pedro Jares, Neus Villamor, Dolors Colomer, José Ignacio Martín-Subero, Elias Campo and Virginia Amador

Key points

  • SOX11 silencing promotes the shift from a mature B-cell into the initial plasmacytic differentiation phenotype in MCL

  • SOX11 promotes tumor growth of MCL cells in vivo highlighting its implication in the aggressive behavior of conventional MCL


Mantle cell lymphoma (MCL) is one of the most aggressive lymphoid neoplasms whose pathogenesis is not fully understood. The neural transcription factor SOX11 is overexpressed in most MCL but is not detected in other mature B-cell lymphomas or normal lymphoid cells. The specific expression of SOX11 in MCL suggests that it may be an important element in the development of this tumor but its potential function is not known. Here, we show that SOX11 promotes tumor growth in a MCL-xenotransplant mouse model. Using ChIP-chip analysis combined with gene expression profiling upon SOX11 knockdown, we identify target genes and transcriptional programs regulated by SOX11 including the block of mature B-cell differentiation, modulation of cell cycle, apoptosis and stem cell development. PAX5 emerges as one of the major SOX11 direct targets. SOX11 silencing downregulates PAX5, induces BLIMP1 expression and promotes the shift from a mature B-cell into the initial plasmacytic differentiation phenotype, in both primary tumor cells and in an in vitro model. Our results suggest that SOX11 contributes to tumor development by altering the terminal B-cell differentiation program of MCL and provide perspectives that may have clinical implications in the diagnosis and design of new therapeutic strategies.

  • Submitted June 25, 2012.
  • Accepted December 10, 2012.