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

J Pathol. 2007 Sep;213(1):106-15. doi: 10.1002/path.2199.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • B-Lymphocytes / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p27
  • Gene Expression
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Genetic Markers
  • Germinal Center / metabolism*
  • Humans
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins / genetics
  • Lymphoma, B-Cell / genetics
  • Lymphoma, B-Cell / metabolism*
  • Lymphoma, Large B-Cell, Diffuse / genetics
  • Lymphoma, Large B-Cell, Diffuse / metabolism
  • Neoplasm Proteins / analysis*
  • Neoplasm Proteins / genetics
  • Oligonucleotide Array Sequence Analysis
  • Positive Regulatory Domain I-Binding Factor 1
  • Proto-Oncogene Proteins c-bcl-6 / analysis
  • Proto-Oncogene Proteins c-bcl-6 / genetics
  • Repressor Proteins / genetics
  • Transcription Factors / genetics

Substances

  • CDKN1B protein, human
  • Genetic Markers
  • Intracellular Signaling Peptides and Proteins
  • MTA3 protein, human
  • Neoplasm Proteins
  • Proto-Oncogene Proteins c-bcl-6
  • Repressor Proteins
  • Transcription Factors
  • PRDM1 protein, human
  • Cyclin-Dependent Kinase Inhibitor p27
  • Positive Regulatory Domain I-Binding Factor 1