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The BCL6‐associated transcriptional co‐repressor, MTA3, is selectively expressed by germinal centre B cells and lymphomas of putative germinal centre derivation
Author(s) -
Jaye DL,
Iqbal J,
Fujita N,
Geigerman CM,
Li S,
Karanam S,
Fu K,
Weisenburger DD,
Chan WC,
Moreno CS,
Wade PA
Publication year - 2007
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2199
Subject(s) - bcl6 , germinal center , biology , repressor , b cell , microbiology and biotechnology , cancer research , gene expression , immunology , gene , genetics , antibody
M e t astasis‐ a ssociated 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.