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Prepublished online as a Blood First Edition Paper on November 21, 2002; DOI 10.1182/blood-2002-07-2215.
Submitted July 23, 2002
Accepted November 6, 2002
Interleukin 4-induced gene 1 (FIG1)is activated in primary mediastinal large B cell lymphoma
Christiane Copie-Bergman, Marie-Laure Boulland, Catherine Dehoulle, Peter Moller, Jean-Pierre Farcet, Martin J S Dyer, Corinne Haioun, Paul-Henri Romeo, Philippe Gaulard, and Karen Leroy*
Departement de Pathologie EA 2348, Hopital Henri Mondor, AP-HP, Creteil, France
Institute of Pathology, University of Ulm, Ulm, Germany
Service d'Immunologie Biologique EA 2348, Hopital Henri Mondor, AP-HP, Creteil, France
Department of Pathology, University of Leicester, Leicester, United Kingdom
Service d'Hematologie Clinique EA 2348, Hopital Henri Mondor, AP-HP, Creteil, France
Departement d'Hematologie, Institut Cochin, Paris, France
* Corresponding author; email: karen.leroy{at}hmn.ap-hop-paris.fr.
The molecular markers that distinguish primary mediastinal large B-cell lymphoma (PMBL) from non-mediastinal diffuse large B-cell lymphomas (NM-DLBLs) remain to be identified. Using cDNA representational difference analysis to compare PMBL and NM-DLBLs transcripts, we isolated a cDNA fragment homologous to the mouse B-cell IL-4-inducible gene FIG1 (Interleukin Four-Induced Gene 1) transcript. The human FIG1 mRNA encodes a 567 amino acid protein that comprises a signal peptide and a large flavin-binding amino oxidase domain, and shares significant homology with secreted apoptosis-inducing L-amino acid oxidases. Northern blot studies showed that FIG1 mRNA expression is mainly restricted to lymphoid tissues. It is expressed at low levels in thymus, spleen, tonsils and reactive lymph nodes, and is highly upregulated in IL-4+CD40 activated tonsillar B-cells. Interestingly, in human B-cell lines, FIG1 mRNA expression appeared restricted to the PMBL-derived MedB-1 and Karpas 1106 cell lines. Using real time RT-PCR, we demonstrated that all but one PMBL (16/17) displayed high FIG1 mRNA levels, whereas most NM-DLBLs (12/18) and all low grade B-cell lymphomas tested (8/8) exhibited low FIG1 mRNA levels. The difference between PMBL and NM-DLBLs was statistically significant (Fisher test; P=0.0003). Southern blot studies did not show rearrangement of the FIG1 gene. FIG1 gene expression might be due to a constitutive activation of a cytokine signaling pathway in PMBL.
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