title: Expression pattern of XBP1(S) in human B-cell lymphomas.
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.
authors.affiliation: Monoclonal Antibodies Unit, Biotechnology Program, Spanish National Cancer Centre (CNIO), Madrid, Spain.
authors.forename: Lorena
authors.initials: L
authors.lastname: Maestre
authors.forename: Reuben
authors.initials: R
authors.lastname: Tooze
authors.forename: Marta
authors.initials: M
authors.lastname: Cañamero
authors.forename: Santiago
authors.initials: S
authors.lastname: Montes-Moreno
authors.forename: Rocio
authors.initials: R
authors.lastname: Ramos
authors.forename: Gina
authors.initials: G
authors.lastname: Doody
authors.forename: May
authors.initials: M
authors.lastname: Boll
authors.forename: Sharon
authors.initials: S
authors.lastname: Barrans
authors.forename: Sara
authors.initials: S
authors.lastname: Baena
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Piris
authors.forename: Giovanna
authors.initials: G
authors.lastname: Roncador
mesh_terms: D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012326:RNA Splicing; D000071701:Regulatory Factor X Transcription Factors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D020298:U937 Cells; D000071717:X-Box Binding Protein 1
chemical_list: D004268:DNA-Binding Proteins; D020033:Protein Isoforms; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human