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

D. L. Jaye, Javeed Iqbal, N. Fujita, C. M. Geigerman, S. Li, S. Karanam, Kai Fu, D. D. Weisenburger, W. C. Chan, C. S. Moreno, P. A. Wade

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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.

Original languageEnglish (US)
Pages (from-to)106-115
Number of pages10
JournalJournal of Pathology
Volume213
Issue number1
DOIs
StatePublished - Sep 1 2007

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Jaye, D. L., Iqbal, J., Fujita, N., Geigerman, C. M., Li, S., Karanam, S., Fu, K., Weisenburger, D. D., Chan, W. C., Moreno, C. S., & Wade, P. A. (2007). The BCL6-associated transcriptional co-repressor, MTA3, is selectively expressed by germinal centre B cells and lymphomas of putative germinal centre derivation. Journal of Pathology, 213(1), 106-115. https://doi.org/10.1002/path.2199