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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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NEOPLASIA
The oncoprotein LMO2 is expressed in normal germinal-center B cells and in human B-cell lymphomas
Yasodha Natkunam1,
Shuchun Zhao1,
David Y. Mason2,
Jun Chen3,
Behnaz Taidi4,
Margaret Jones2,
Anne S. Hammer5,
Stephen Hamilton Dutoit5,
Izidore S. Lossos3, and
Ronald Levy4
1 Department of Pathology, Stanford University School of Medicine, CA;
2 Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, Oxford, United Kingdom;
3 Division of Hematology-Oncology, Department of Medicine, Sylvester Comprehensive Cancer Center, and Department of Molecular and Cellular Pharmacology, University of Miami, FL;
4 Department of Medicine, Division of Oncology, Stanford University School of Medicine, CA;
5 Institute of Pathology, Aarhus University Hospital, Denmark
We previously developed a multivariate model based on the RNA expression of 6 genes (LMO2, BCL6, FN1, CCND2, SCYA3, and BCL2) that predicts survival in diffuse large B-cell lymphoma (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. Immunohistologic 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 and 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, natural killer (NK), and plasma cell neoplasms and was absent from nonhematolymphoid 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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