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

被引:130
作者
Natkunam, Yasodha
Zhao, Shuchun
Mason, David Y.
Chen, Jun
Taidi, Behnaz
Jones, Margaret
Hammer, Anne S.
Dutoit, Stephen Hamilton
Lossos, Izidore S.
Levy, Ronald
机构
[1] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA
[2] John Radcliffe Hosp, Nuffield Dept Clin Lab Sci, Oxford OX3 9DU, England
[3] Univ Miami, Sylvester Comprehens Canc Ctr, Dept Med, Div Hematol Oncol, Miami, FL 33152 USA
[4] Univ Miami, Dept Mol & Cellular Pharmacol, Miami, FL 33152 USA
[5] Stanford Univ, Sch Med, Dept Med, Div Oncol, Stanford, CA 94305 USA
[6] Aarhus Univ Hosp, Inst Pathol, DK-8000 Aarhus, Denmark
关键词
D O I
10.1182/blood-2006-08-039024
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. Immumohistologic 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 erythrold 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 nonhernatolymphoid tissues except for endothelial cells. Hierarchical cluster analysis of immunolhistologic 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/ARF4 and BCL2). Our results warrant inclusion of LMO2 in multivariate analyses to construct a clinically applicable immumohistologic algorithm for predicting survival in patients with DLBCL.
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收藏
页码:1636 / 1642
页数:7
相关论文
共 32 条
[1]   Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling [J].
Alizadeh, AA ;
Eisen, MB ;
Davis, RE ;
Ma, C ;
Lossos, IS ;
Rosenwald, A ;
Boldrick, JG ;
Sabet, H ;
Tran, T ;
Yu, X ;
Powell, JI ;
Yang, LM ;
Marti, GE ;
Moore, T ;
Hudson, J ;
Lu, LS ;
Lewis, DB ;
Tibshirani, R ;
Sherlock, G ;
Chan, WC ;
Greiner, TC ;
Weisenburger, DD ;
Armitage, JO ;
Warnke, R ;
Levy, R ;
Wilson, W ;
Grever, MR ;
Byrd, JC ;
Botstein, D ;
Brown, PO ;
Staudt, LM .
NATURE, 2000, 403 (6769) :503-511
[2]   Age-related phenotypic and oncogenic differences in T-cell acute lymphoblastic leukemias may reflect thymic atrophy [J].
Asnafi, V ;
Beldjord, K ;
Libura, M ;
Villarese, P ;
Millien, C ;
Ballerini, P ;
Kuhlein, E ;
Lafage-Pochitaloff, M ;
Delabesse, E ;
Bernard, O ;
Macintyre, E .
BLOOD, 2004, 104 (13) :4173-4180
[3]   The LIM domain: regulation by association [J].
Bach, I .
MECHANISMS OF DEVELOPMENT, 2000, 91 (1-2) :5-17
[4]   Germinal center phenotype and bcl-2 expression combined with the International Prognostic Index improves patient risk stratification in diffuse large B-cell lymphoma [J].
Barrans, SL ;
Carter, I ;
Owen, RG ;
Davies, FE ;
Patmore, RD ;
Haynes, AP ;
Morgan, GJ ;
Jack, AS .
BLOOD, 2002, 99 (04) :1136-1143
[5]   Diffuse large B-cell lymphoma subgroups have distinct genetic profiles that influence tumor biology and improve gene-expression-based survival prediction [J].
Bea, S ;
Zettl, A ;
Wright, G ;
Salaverria, I ;
Jehn, P ;
Moreno, V ;
Burek, C ;
Ott, G ;
Puig, X ;
Yang, LM ;
Lopez-Guillermo, A ;
Chan, WC ;
Greiner, TC ;
Weisenburger, DD ;
Armitage, JO ;
Gascoyne, RD ;
Connors, JM ;
Grogan, TM ;
Braziel, R ;
Fisher, RI ;
Smeland, EB ;
Kvaloy, S ;
Holte, H ;
Delabie, J ;
Simon, R ;
Powell, J ;
Wilson, WH ;
Jaffe, ES ;
Montserrat, E ;
Muller-Hermelink, HK ;
Staudt, LM ;
Campo, E ;
Rosenwald, A .
BLOOD, 2005, 106 (09) :3183-3190
[6]   THE RHOMBOTIN FAMILY OF CYSTEINE-RICH LIM-DOMAIN ONCOGENES - DISTINCT MEMBERS ARE INVOLVED IN T-CELL TRANSLOCATIONS TO HUMAN CHROMOSOME-11P15 AND CHROMOSOME-11P13 [J].
BOEHM, T ;
FORONI, L ;
KANEKO, Y ;
PERUTZ, MF ;
RABBITTS, TH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (10) :4367-4371
[7]   MOUSE X HUMAN HETEROHYBRIDOMAS AS FUSION PARTNERS WITH HUMAN B-CELL TUMORS [J].
CARROLL, WL ;
THIELEMANS, K ;
DILLEY, J ;
LEVY, R .
JOURNAL OF IMMUNOLOGICAL METHODS, 1986, 89 (01) :61-72
[8]   Clinical impact of the differentiation profile assessed by immunophenotyping in patients with diffuse large B-cell lymphoma [J].
Colomo, L ;
Löpez-Guillermo, A ;
Perales, M ;
Rives, S ;
Martínez, A ;
Bosch, F ;
Colomer, D ;
Falini, B ;
Montserrat, E ;
Campo, E .
BLOOD, 2003, 101 (01) :78-84
[9]   Expression of rhombotin 2 in normal and leukaemic haemopoietic cells [J].
Dong, WF ;
Billia, F ;
Atkins, HL ;
Iscove, NN ;
Minden, MD .
BRITISH JOURNAL OF HAEMATOLOGY, 1996, 93 (02) :280-286
[10]   Biallelic transcriptional activation of oncogenic transcription factors in T-cell acute lymphoblastic leukemia [J].
Ferrando, AA ;
Herblot, S ;
Palomero, T ;
Hansen, M ;
Hoang, T ;
Fox, EA ;
Look, AT .
BLOOD, 2004, 103 (05) :1909-1911