The BCL6‐associated transcriptional co‐repressor, MTA3, is selectively expressed by germinal centre B cells and lymphomas of putative germinal centre derivation

Publisher Website
Google Scholar
Abstract
Metastasis‐associated protein 3 (MTA3) is a recently described cell‐type specific component of the Mi‐2‐NURD transcriptional co‐repressor complex that is expressed in breast epithelia and germinal centre B cells. In model B cell lines, MTA3 physically interacts with BCL6 and appears to be instrumental in maintenance of the germinal centre B cell transcriptional programme that precludes premature plasmacytic differentiation. Here, we report selective, in situ cell‐type specific expression of MTA3 among lymphoid cells largely confined to the germinal centre B cell compartment. Centroblasts display greater expression than smaller, less proliferative centrocytes, with undetectable expression in quiescent plasma cells. Among B cell neoplasms, germinal centre B cell‐like lymphomas likewise exhibit selective expression that generally escalates with increasing proliferative capacity. MTA3 protein expression was, in accord, highly predictive of the germinal centre B cell‐like gene expression profile for diffuse large B cell lymphomas. Lastly, relative repression of a subset of known BCL6 targets, including BLIMP1 and p27kip1, was highest in diffuse large B cell lymphomas that co‐expressed both MTA3 and BCL6 protein. Together, these novel data suggest a role for MTA3 in BCL6‐mediated lymphomagenesis in germinal centre B cell‐like neoplasms. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.