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 GCderived 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.

OTX1 expression in breast cancer is regulated by p53

“…differentiation as a tumor suppression mechanism. The OTX1 nuclear and/or cytoplasmic localization suggest different functions of this molecule in cell differentiation (Zhang et al, 2002;Omodei et al, 2009). Additional data show different OTX1 gene expression levels in mice breast tissues during the linear and the cyclical organ phases, suggesting its function in normal stem cell differentiation.…”

Aberrantly Expressed OTX Homeobox Genes Deregulate B-Cell Differentiation in Hodgkin Lymphoma

“…While OTX1 expression has been described in small subsets of normal germinal center B-cells in addition to high levels in subsets of aggressive non-HL, OTX2 was detected neither in normal B-cells nor in B-cell lymphomas [ 42 , 43 ]. Although we have identified ectopic expression of OTX2 just in subsets of HL this homeobox gene may deregulate general oncogenic targets or pathways and thus contribute to lymphomagenesis.…”

Biological functions of p53 isoforms through evolution: lessons from animal and cellular models

“…Conservation in constitutively spliced exons is more prominent for the ESEs recognizing SF2/ASF and SF2/ASF(IgM-BRCA1) which are primarily responsible for splicing. On the contrary, ESEs recognizing SRp40 and SRp55, involved in the regulation of cellular response to intra-and extracellular conditions [2,3] are less conserved (this is also observed between the mouse and rat p53 sequences). Smaller differences in the ESE distribution are observed in exons 7 and 8.…”