Brief Reports |
1 Monoclonal Antibodies Unit, Biotechnology Program, Spanish National Cancer Centre (CNIO), Madrid, Spain;
2 Section of Experimental Haematology, Leeds Institute of Molecular Medicine, St Jamess University Hospital, Leeds, UK;
3 Haematological Malignancy Diagnostic Service, Leeds Teaching Hospitals NHS Trust, St Jamess 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.