The pre-B-cell receptor associated protein VpreB3 is a useful diagnostic marker for identifying c-MYC translocated lymphomas.
BACKGROUND
During B-cell development, precursor B cells transiently express the pre-B-cell receptor composed of μ 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.


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 translocation (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.
Rodig
Scott J
SJ
Department of Pathology, Brigham & Women's Hospital, Boston, MA, USA.
Kutok
Jeffery L
JL
Paterson
Jennifer C
JC
Nitta
Hiroaki
H
Zhang
Wenjun
W
Chapuy
Bjoern
B
Tumwine
Lynette K
LK
Montes-Moreno
Santiago
S
Agostinelli
Claudio
C
Johnson
Nathalie A
NA
Ben-Neriah
Susana
S
Farinha
Pedro
P
Shipp
Margaret A
MA
Piris
Miguel A
MA
Grogan
Thomas M
TM
Pileri
Stefano A
SA
Gascoyne
Randy D
RD
Marafioti
Teresa
T
D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002051:Burkitt Lymphoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D018858:Germinal Center / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D054420:Pre-B Cell Receptors / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D016019:Survival Analysis
D014408:Biomarkers, Tumor; C489427:MYC protein, human; D054420:Pre-B Cell Receptors; D016271:Proto-Oncogene Proteins c-myc; C515476:pre-B lymphocyte protein 3, human
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