The pre-B-cell receptor associated protein VpreB3 is a useful diagnostic marker for identifying c-MYC translocated lymphomas

Abstract

The online version of this article has a Supplementary Appendix. Background During B-cell development, precursor B cells transiently express the pre-B-cell receptor composed of m heavy chain complexed with VpreB and λ5 surrogate light chain polypeptides. Recent profiling studies unexpectedly revealed abundant transcripts of one member of the VpreB family, VpreB3, in a subset of mature B cells and Burkitt lymphoma. Design and Methods Here we used a novel antibody to investigate the normal expression pattern of VpreB3 protein in human hematopoietic and lymphoid tissues, and to determine whether VpreB3 could serve as a useful diagnostic biomarker for select B-cell lymphomas. Results We found that VpreB3 protein is normally expressed by precursor B cells in bone marrow and by a subset of normal germinal center B cells in secondary lymphoid organs. Among lymphoid malignancies, we found an association between VpreB3 expression and B-cell tumors with c-MYC abnormalities. VpreB3 was highly expressed in all cases of Burkitt lymphoma, whether of endemic or sporadic origin (44/44 cases, 100%), all cases of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (5/5 cases, 100%), and the majority of diffuse large B-cell lymphomas harboring a c-MYC translo-cation (15/18 cases, 83%). The expression of VpreB3 in diffuse large B-cell lymphomas without a c-MYC translocation was associated with c-MYC polysomy in 25/75 cases (33%) but only rarely observed in diffuse large B-cell lymphomas lacking a c-MYC abnormality (9/98 cases, 9%). Conclusions We conclude that for B-cell tumors with features suggesting a possible c-MYC translocation, such as intermediate to large cell size and high proliferation rate, the presence of VpreB3 should prompt subsequent confirmatory genetic testing, whereas the absence of VpreB3 is virtually always associated with wild-type c-MYC alleles. ABSTRACT 2056 haematologica | 2010; 95(12)

The combined expression of VPREB3 and ID3 represents a new helpful tool for the routine diagnosis of mature aggressive B‐cell lymphomas

“…Recently, Rodig et al . reported VPREB3 expression in all BL and intermediate BL/DLBCL cases and in 82% of DLBCL showing a MYC aberration . In our cohort, in contrast, 9.1% BL and 19.2% intermediate BL/DLBCL were negative for VPREB3, which, however, is in line with results of NGS and GEP studies .…”

Immunohistochemical detection of MYC protein correlates with MYC gene status in aggressive B cell lymphomas

“…Recently, Rodig et al. 10 have reported that VpreB3 expression as detected by immunohistochemistry could be useful as a screening tool for predicting MYC gene translocation, although the antibody they used is not commercially available.…”

“…Regarding the cell of origin, Barrans et al 9 found a significantly higher frequency of GC-like phenotype in MYC + DLBCL, although Savage et al 8 did not find such association. Recently, Rodig et al 10 have reported that VpreB3 expression as detected by immunohistochemistry could be useful as a screening tool for predicting MYC gene translocation, although the antibody they used is not commercially available.…”

“…In this context, the feasibility of an immunohistochemical stain able to predict the status of the MYC gene would be very useful. Recently, it has been reported that the presence of the VpreB3 protein alone could be a useful marker in predicting MYC + DLBCL, although unfortunately the polyclonal antibody used in this study is not commercially available 10 . We wanted to investigate whether the presence of the MYC protein, detected by immunohistochemistry with commercially available antibodies, correlated with the gene status and could be used as a screening tool.…”

Diffuse large B-cell lymphoma and Burkitt lymphoma

“…VpreB3, a protein in the pre-B-cell receptor, is highly expressed in all cases of Burkitt lymphoma ( Figure 5), whether of endemic or sporadic origin, B-UNC/BL/DLBC and the majority of diffuse large B-cell lymphomas harbouring a c-MYC translocation. 24 Although >90% of African BL cases are positive for EBV, only about 30% of cases in Western areas contain EBV.…”