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

Scott J. Rodig, Jeffery L. Kutok, Jennifer C. Paterson, Hiroaki Nitta, Wenjun Zhang, Bjoern Chapuy, Lynette K. Tumwine, Santiago Montes-Moreno, Claudio Agostinelli, Nathalie A. Johnson, Susana Ben-Neriah, Pedro Farinha, Margaret A. Shipp, Miguel A. Piris, Thomas M. Grogan, Stefano A. Pileri, Randy D. Gascoyne, Teresa Marafioti

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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. 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 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.

Original languageEnglish
Pages (from-to)2056-2062
Number of pages7
JournalHaematologica
Volume95
Issue number12
DOIs
Publication statusPublished - Dec 2010

Fingerprint

Pre-B Cell Receptors
Lymphoma, Large B-Cell, Diffuse
Burkitt Lymphoma
Lymphoma
B-Cell Lymphoma
B-Lymphocytes
B-Lymphoid Precursor Cells
Surrogate Immunoglobulin Light Chains
Proteins
Neoplasms
Germinal Center
Genetic Testing
Lymphoid Tissue
Cell Size
Biomarkers
Bone Marrow
Alleles
Peptides
Antibodies

Keywords

  • Burkitt lymphoma
  • C-Myc
  • Diffuse large B-cell lymphoma
  • Immunohistochemistry
  • Lymphoma
  • Pre-BCR
  • VpreB3

ASJC Scopus subject areas

  • Hematology

Cite this

Rodig, S. J., Kutok, J. L., Paterson, J. C., Nitta, H., Zhang, W., Chapuy, B., ... Marafioti, T. (2010). The pre-B-cell receptor associated protein VpreB3 is a useful diagnostic marker for identifying c-MYC translocated lymphomas. Haematologica, 95(12), 2056-2062. https://doi.org/10.3324/haematol.2010.025767

The pre-B-cell receptor associated protein VpreB3 is a useful diagnostic marker for identifying c-MYC translocated lymphomas. / Rodig, Scott J.; Kutok, Jeffery L.; Paterson, Jennifer C.; Nitta, Hiroaki; Zhang, Wenjun; Chapuy, Bjoern; Tumwine, Lynette K.; Montes-Moreno, Santiago; Agostinelli, Claudio; Johnson, Nathalie A.; Ben-Neriah, Susana; Farinha, Pedro; Shipp, Margaret A.; Piris, Miguel A.; Grogan, Thomas M.; Pileri, Stefano A.; Gascoyne, Randy D.; Marafioti, Teresa.

In: Haematologica, Vol. 95, No. 12, 12.2010, p. 2056-2062.

Research output: Contribution to journalArticle

Rodig, SJ, Kutok, JL, Paterson, JC, Nitta, H, Zhang, W, Chapuy, B, Tumwine, LK, Montes-Moreno, S, Agostinelli, C, Johnson, NA, Ben-Neriah, S, Farinha, P, Shipp, MA, Piris, MA, Grogan, TM, Pileri, SA, Gascoyne, RD & Marafioti, T 2010, 'The pre-B-cell receptor associated protein VpreB3 is a useful diagnostic marker for identifying c-MYC translocated lymphomas', Haematologica, vol. 95, no. 12, pp. 2056-2062. https://doi.org/10.3324/haematol.2010.025767
Rodig, Scott J. ; Kutok, Jeffery L. ; Paterson, Jennifer C. ; Nitta, Hiroaki ; Zhang, Wenjun ; Chapuy, Bjoern ; Tumwine, Lynette K. ; Montes-Moreno, Santiago ; Agostinelli, Claudio ; Johnson, Nathalie A. ; Ben-Neriah, Susana ; Farinha, Pedro ; Shipp, Margaret A. ; Piris, Miguel A. ; Grogan, Thomas M. ; Pileri, Stefano A. ; Gascoyne, Randy D. ; Marafioti, Teresa. / The pre-B-cell receptor associated protein VpreB3 is a useful diagnostic marker for identifying c-MYC translocated lymphomas. In: Haematologica. 2010 ; Vol. 95, No. 12. pp. 2056-2062.
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abstract = "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. 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 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.",
keywords = "Burkitt lymphoma, C-Myc, Diffuse large B-cell lymphoma, Immunohistochemistry, Lymphoma, Pre-BCR, VpreB3",
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T1 - The pre-B-cell receptor associated protein VpreB3 is a useful diagnostic marker for identifying c-MYC translocated lymphomas

AU - Rodig, Scott J.

AU - Kutok, Jeffery L.

AU - Paterson, Jennifer C.

AU - Nitta, Hiroaki

AU - Zhang, Wenjun

AU - Chapuy, Bjoern

AU - Tumwine, Lynette K.

AU - Montes-Moreno, Santiago

AU - Agostinelli, Claudio

AU - Johnson, Nathalie A.

AU - Ben-Neriah, Susana

AU - Farinha, Pedro

AU - Shipp, Margaret A.

AU - Piris, Miguel A.

AU - Grogan, Thomas M.

AU - Pileri, Stefano A.

AU - Gascoyne, Randy D.

AU - Marafioti, Teresa

PY - 2010/12

Y1 - 2010/12

N2 - 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. 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 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.

AB - 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. 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 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.

KW - Burkitt lymphoma

KW - C-Myc

KW - Diffuse large B-cell lymphoma

KW - Immunohistochemistry

KW - Lymphoma

KW - Pre-BCR

KW - VpreB3

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