title: The oncoprotein LMO2 is expressed in normal germinal-center B cells and in human B-cell lymphomas.
abstract: 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.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, CA, USA, and Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, Oxford, UK. yaso@stanford.edu
authors.forename: Yasodha
authors.initials: Y
authors.lastname: Natkunam
authors.forename: Shuchun
authors.initials: S
authors.lastname: Zhao
authors.forename: David Y
authors.initials: DY
authors.lastname: Mason
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Behnaz
authors.initials: B
authors.lastname: Taidi
authors.forename: Margaret
authors.initials: M
authors.lastname: Jones
authors.forename: Anne S
authors.initials: AS
authors.lastname: Hammer
authors.forename: Stephen
authors.initials: S
authors.lastname: Hamilton Dutoit
authors.forename: Izidore S
authors.initials: IS
authors.lastname: Lossos
authors.forename: Ronald
authors.initials: R
authors.lastname: Levy
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D001402:B-Lymphocytes / Q000737:chemistry*; D002460:Cell Line; D016000:Cluster Analysis; D004268:DNA-Binding Proteins / Q000032:analysis*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D018858:Germinal Center; D006801:Humans; D007150:Immunohistochemistry; D060588:LIM Domain Proteins; D016393:Lymphoma, B-Cell / Q000737:chemistry*; D016403:Lymphoma, Large B-Cell, Diffuse; D008667:Metalloproteins / Q000032:analysis*; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000032:analysis; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; C085117:LMO2 protein, human; D008667:Metalloproteins; D011518:Proto-Oncogene Proteins