title: The BCL6-associated transcriptional co-repressor, MTA3, is selectively expressed by germinal centre B cells and lymphomas of putative germinal centre derivation.
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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA. dljaye@emory.edu
authors.forename: D L
authors.initials: DL
authors.lastname: Jaye
authors.forename: J
authors.initials: J
authors.lastname: Iqbal
authors.forename: N
authors.initials: N
authors.lastname: Fujita
authors.forename: C M
authors.initials: CM
authors.lastname: Geigerman
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.forename: S
authors.initials: S
authors.lastname: Karanam
authors.forename: K
authors.initials: K
authors.lastname: Fu
authors.forename: D D
authors.initials: DD
authors.lastname: Weisenburger
authors.forename: W C
authors.initials: WC
authors.lastname: Chan
authors.forename: C S
authors.initials: CS
authors.lastname: Moreno
authors.forename: P A
authors.initials: PA
authors.lastname: Wade
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers; D018858:Germinal Center / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000032:analysis* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D000074462:Positive Regulatory Domain I-Binding Factor 1; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000032:analysis / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
chemical_list: C436291:CDKN1B protein, human; D005819:Genetic Markers; D047908:Intracellular Signaling Peptides and Proteins; C486657:MTA3 protein, human; D009363:Neoplasm Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D012097:Repressor Proteins; D014157:Transcription Factors; C087042:PRDM1 protein, human; D050760:Cyclin-Dependent Kinase Inhibitor p27; D000074462:Positive Regulatory Domain I-Binding Factor 1