title: Expression of the brain transcription factor OTX1 occurs in a subset of normal germinal-center B cells and in aggressive Non-Hodgkin Lymphoma.
abstract: The roles in brain development. Previous studies have shown the association between OTX2 and OTX1 with anaplastic and desmoplastic medulloblastomas, respectively. Here, we investigated OTX1 and OTX2 expression in Non-Hodgkin Lymphoma (NHL) and multiple myeloma. A combination of semiquantitative RT-PCR, Western blot, and immunohistochemical analyses was used to measure OTX1 and OTX2 levels in normal lymphoid tissues and in 184 tumor specimens representative of various forms of NHL and multiple myeloma. OTX1 expression was activated in 94% of diffuse large B-cell lymphomas, in all Burkitt lymphomas, and in 90% of high-grade follicular lymphomas. OTX1 was undetectable in precursor-B lymphoblastic lymphoma, chronic lymphocytic leukemia, and in most marginal zone and mantle cell lymphomas and multiple myeloma. OTX2 was undetectable in all analyzed malignancies. Analysis of OTX1 expression in normal lymphoid tissues identified a subset of resting germinal center (GC) B cells lacking PAX5 and BCL6 and expressing cytoplasmic IgG and syndecan. About 50% of OTX1(+) GC B cells co-expressed CD10 and CD20. This study identifies OTX1 as a molecular marker for high-grade GC-derived NHL and suggests an involvement of this transcription factor in B-cell lymphomagenesis. Furthermore, OTX1 expression in a subset of normal GC B cells carrying plasma cell markers suggests its possible contribution to terminal B-cell differentiation.
authors.affiliation: Centro di Ingegneria Genetica (CEINGE) Biotecnologie Avanzate, Naples, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Omodei
authors.forename: Dario
authors.initials: D
authors.lastname: Acampora
authors.forename: Filippo
authors.initials: F
authors.lastname: Russo
authors.forename: Rosaria
authors.initials: R
authors.lastname: De Filippi
authors.forename: Valeria
authors.initials: V
authors.lastname: Severino
authors.forename: Raffaele
authors.initials: R
authors.lastname: Di Francia
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Frigeri
authors.forename: Pietro
authors.initials: P
authors.lastname: Mancuso
authors.forename: Anna
authors.initials: A
authors.lastname: De Chiara
authors.forename: Antonio
authors.initials: A
authors.lastname: Pinto
authors.forename: Stefano
authors.initials: S
authors.lastname: Casola
authors.forename: Antonio
authors.initials: A
authors.lastname: Simeone
mesh_terms: D016175:B-Lymphocyte Subsets / Q000378:metabolism*; D001402:B-Lymphocytes / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D018858:Germinal Center / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism*; D009101:Multiple Myeloma / Q000378:metabolism; D051857:Otx Transcription Factors / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; C497655:OTX1 protein, human; C497659:OTX2 protein, human; D051857:Otx Transcription Factors