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Blood, 15 February 2007, Vol. 109, No. 4, pp. 1636-1642.
Prepublished online as a Blood First Edition Paper on October 12, 2006; DOI 10.1182/blood-2006-08-039024.
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Submitted August 1, 2006
Accepted October 3, 2006
The oncoprotein LMO2 is expressed in normal germinal center B-cells and in human B-cell lymphomas
Yasodha Natkunam*, Shuchun Zhao, David Y. Mason, Jun Chen, Behnaz Taidi, Margaret Jones, Anne S Hammer, Stephen Hamilton-Dutoit, Izidore S. Lossos, and Ronald Levy
Dept of Pathology, Stanford University School of Medicine, Stanford, CA
Nuffield Dept of Clinical Laboratory Sciences, John Radcliffe Hospital, Oxford, United Kingdom
Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL
Dept of Medicine, Division of Oncology, Stanford University School of Medicine, Stanford, CA
Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark
* Corresponding author; email: yaso{at}stanford.edu.
We previously developed a multivariate model based on the RNA expression of six genes - LMO2, BCL6, FN1, CCND2, SCYA3 and BCL2 - that predicts survival in DLBCL patients. Since LMO2 emerged as the strongest predictor of superior outcome, we generated a monoclonal anti-LMO2 antibody in order to study its tissue expression pattern. Immunohistological analysis of over 1200 normal and neoplastic tissue and cell-lines showed that LMO2 protein is expressed as a nuclear marker in normal germinal center (GC) B-cells, GC-derived B-cell lines and in a subset of GC-derived B-cell lymphomas. LMO2 was also expressed in erythroid and myeloid precursors and in megakaryocytes, and also in lymphoblastic and acute myeloid leukemias. It was rarely expressed in mature T, NK and plasma cell neoplasms and was absent from non-hematolymphoid tissues except for endothelial cells. Hierarchical cluster analysis of immunohistologic data in DLBCL demonstrated that the expression profile of the LMO2 protein was similar to that of other GC-associated proteins (HGAL, BCL6 and CD10) but different from that of non-GC proteins (MUM1/IRF4 and BCL2). Our results warrant inclusion of LMO2 in multivariate analyses to construct a clinically applicable immunohistologic algorithm for predicting survival in patients with DLBCL.
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