VpreB3, a Pre-BCR Associated Protein, Is Expressed by a Subset of Mature, Germinal Center B Cells and a Biomarker of Burkitt Lymphoma
SJ Rodig, JL Kutok, JC Paterson, W Zhang, MA Shipp, T Grogan, SA Pileri, S Montes-Moreno, NA Johnson, S Ben-Neriah, P Farinha, MA Piris, R Gascoyne, T Marafioti. Brigham and Women's Hospital, Boston, MA; University of Oxford, Oxford, United Kingdom; Ventana Medical Systems, Tucson, AZ; Dana-Farber Cancer Institute, Boston, MA; University of Arizona, Tucson, AZ; Bologna University School of Medicine, Bologna, Italy; Spanish National Cancer Centre (CNIO), Madrid, Spain; British Columbia Cancer Agency, Vancouve, Canada
Background: During B cell development, precursor B cells transiently express the pre-B cell receptor that is composed of μ heavy chain complexed with VpreB and λ5 surrogate light chain polypeptides. Recent profiling studies have unexpectedly revealed abundant transcripts of one member of the VpreB family, VpreB3, in a subset of mature B cell lymphomas.
Design: We used a novel antibody examine VpreB3 expression in normal human hematopoietic and lymphoid tissues and in 610 hematolymphoid malignancies by standard immunohistochemistry. All cases were scored by two hematopathologists in a blinded fashion.
Results: Whereas VpreB3 protein is restricted to precursor B cells within the bone marrow, we find that VpreB3 protein is highly expressed by a subset of normal germinal center B cells- especially within the proliferative dark zone. Among lymphoid malignancies, VpreB3 is expressed in a subset of B-lymphoblastic lymphomas (4 of 10 cases, 40%) but in all cases of Burkitt lymphoma, whether of endemic or sporatic origin (49 of 49 cases, 100%). In contrast, VpreB3 is expressed in only a minority of diffuse large B cell lymphomas (49 of 191 cases, 26%) and other B cell lymphomas. A detailed examination of VpreB3 positive diffuse large B cell lymphomas revealed that the vast majority (40 of 49 cases, 82%) exhibit either a translocation or polysomy involving the c-MYC locus.
Conclusions: Our findings suggest a biologic role for VpreB3 beyond early B cell development and establish VpreB3 as a novel, highly sensitive biomarker for distinguishing Burkitt lymphoma from diffuse large B cell lymphoma (sensitivity= 100%, specificity= 74%), that is likely regulated by c-MYC.
Monday, March 22, 2010 8:00 AM
Platform Session: Section B, Monday Morning