The oncoprotein LMO2 is expressed in normal germinal center B-cells and in human B-cell lymphomas

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BlankBlood First Edition Paper, prepublished online October 12, 2006; DOI

10.1182/blood-2006-08-039024.

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, Y. Mason, Jun Chen, Behnaz Taidi,

Margaret , Anne S Hammer, Hamilton-Dutoit, Izidore S. Lossos, and

Levy

Dept of Pathology, Stanford University School of Medicine, Stanford, CA

Nuffield Dept of Clinical Laboratory Sciences, 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@... .

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.