Published online 27 January 2009
Haematologica, Vol 94, Issue 3, 419-422 doi:10.3324/haematol.2008.001156
Copyright © 2009 by Ferrata Storti Foundation
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Brief Reports

Expression pattern of XBP1(S) in human B-cell lymphomas

Lorena Maestre1, Reuben Tooze2,3, Marta Cañamero4, Santiago Montes-Moreno5, Rocio Ramos1, Gina Doody2, May Boll3, Sharon Barrans3, Sara Baena1, Miguel Angel Piris5, Giovanna Roncador1

1 Monoclonal Antibodies Unit, Biotechnology Program, Spanish National Cancer Centre (CNIO), Madrid, Spain;
2 Section of Experimental Haematology, Leeds Institute of Molecular Medicine, St James’s University Hospital, Leeds, UK;
3 Haematological Malignancy Diagnostic Service, Leeds Teaching Hospitals NHS Trust, St James’s University Hospital, Leeds, UK;
4 Comparative Pathology Unit, Biotechnology Program, Spanish National Cancer Centre (CNIO), Madrid, Spain;
5 Lymphoma Group, Molecular Pathology Program, Spanish National Cancer Centre (CNIO), Madrid, Spain

Correspondence: Giovanna Roncador, Monoclonal Antibodies Unit, Biotechnology Program, Centro Nacional de Investigaciones Oncologicas (Spanish National Cancer Centre) C/Melchor Fernández Almagro 3, E-28029 Madrid, Spain., E-mail:groncador{at}cnio.es

ABSTRACT

The transcription factor XBP1 (X-box-binding protein 1) is essential for plasma cell (PC) differentiation and immunoglobulin secretion. XBP1 is widely expressed, but its activity is precisely controlled by mRNA splicing in response to endoplasmic reticulum (ER) stress. It is the active form of XBP1, XBP1(S), which is required for PC differentiation. The relationship between XBP1(S) expression and PC differentiation in human tissue and its expression in hematologic malignancies has eluded assessment. With a novel antibody, we now define XBP1(S) expression in a large series of normal and neoplastic lymphoid tissues. We establish that XBP1(S) provides a specific marker of advanced plasma differentiation and in lymphoid malignancies is restricted to PC-derived neoplasms and plasmablastic diffuse large B-cell lymphomas. XBP1(S) expression delineates heterogeneity amongst plasmablastic diffuse large B-cell lymphomas, identifying a distinct tumor sub-group. Furthermore, our results establish a direct and practical means of assessing ER stress in human tumors.

Key words: plasma cell, lymphomas, XBPS1(s), monoclonal antibody.