Renée Beekman1,2, Virginia Amador1,2, Elias Campo1,2,3. 1. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona. 2. Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid. 3. Hematopathology Section, Laboratory of Pathology, Hospital Clínic of Barcelona, University of Barcelona, Barcelona, Spain.
Abstract
PURPOSE OF REVIEW: SOX11 has emerged as a key transcription factor in the pathogenesis of mantle cell lymphoma (MCL) whereas it is not expressed in normal B cells or virtually in any other mature B-cell neoplasm. This review will examine the role of SOX11 as a biomarker in MCL, the new information on its transcriptional targets, and the mechanisms regulating its expression in MCL. RECENT FINDINGS: SOX11 is highly expressed in conventional MCL, including cyclin D1-negative cases, but it is not expressed in the indolent leukemic nonnodal MCL subtype. These two MCL subtypes also differ in their cell-of-origin, IGHV mutational status and genomic instability. SOX11 promotes tumor growth of MCL cells in vivo and regulates a broad transcriptional program that includes B-cell differentiation pathways and tumor-microenvironment interactions, among others. The mechanisms upregulating SOX11 in MCL are not well understood but are mediated in part by the three-dimensional reconfiguration of the DNA, bringing together a distant enhancer region and the SOX11 promoter. SUMMARY: SOX11 is a relevant element in the pathogenesis of MCL and has been instrumental to identify two distinct clinicobiological subtypes of this tumor. Further studies should clarify the mechanisms mediating its oncogenic potential and leading to its intriguing expression in these tumors.
PURPOSE OF REVIEW: SOX11 has emerged as a key transcription factor in the pathogenesis of mantle cell lymphoma (MCL) whereas it is not expressed in normal B cells or virtually in any other mature B-cell neoplasm. This review will examine the role of SOX11 as a biomarker in MCL, the new information on its transcriptional targets, and the mechanisms regulating its expression in MCL. RECENT FINDINGS:SOX11 is highly expressed in conventional MCL, including cyclin D1-negative cases, but it is not expressed in the indolent leukemic nonnodal MCL subtype. These two MCL subtypes also differ in their cell-of-origin, IGHV mutational status and genomic instability. SOX11 promotes tumor growth of MCL cells in vivo and regulates a broad transcriptional program that includes B-cell differentiation pathways and tumor-microenvironment interactions, among others. The mechanisms upregulating SOX11 in MCL are not well understood but are mediated in part by the three-dimensional reconfiguration of the DNA, bringing together a distant enhancer region and the SOX11 promoter. SUMMARY:SOX11 is a relevant element in the pathogenesis of MCL and has been instrumental to identify two distinct clinicobiological subtypes of this tumor. Further studies should clarify the mechanisms mediating its oncogenic potential and leading to its intriguing expression in these tumors.
Authors: Pieter Van Vlierberghe; Steven Goossens; Tim Pieters; Sara T'Sas; Stijn Vanhee; André Almeida; Yasmine Driege; Juliette Roels; Wouter Van Loocke; Willem Daneels; Mathijs Baens; Arnaud Marchand; Maaike Van Trimpont; Filip Matthijssens; Julie Morscio; Kelly Lemeire; Béatrice Lintermans; Lindy Reunes; Patrick Chaltin; Fritz Offner; Jo Van Dorpe; Tino Hochepied; Geert Berx; Rudi Beyaert; Jens Staal Journal: J Exp Med Date: 2021-08-18 Impact factor: 14.307
Authors: Roser Vilarrasa-Blasi; Paula Soler-Vila; Núria Verdaguer-Dot; Núria Russiñol; Marco Di Stefano; Vicente Chapaprieta; Guillem Clot; Irene Farabella; Pol Cuscó; Marta Kulis; Xabier Agirre; Felipe Prosper; Renée Beekman; Silvia Beà; Dolors Colomer; Hendrik G Stunnenberg; Ivo Gut; Elias Campo; Marc A Marti-Renom; José Ignacio Martin-Subero Journal: Nat Commun Date: 2021-01-28 Impact factor: 14.919