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Prepublished online as a Blood First Edition Paper on November 21, 2002; DOI 10.1182/blood-2002-07-2215.
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Blood, 1 April 2003, Vol. 101, No. 7, pp. 2756-2761
NEOPLASIA
Interleukin 4-induced gene 1 is activated in primary mediastinal
large B-cell lymphoma
Christiane Copie-Bergman,
Marie-Laure Boulland,
Catherine Dehoulle,
Peter Möller,
Jean-Pierre Farcet,
Martin J. S. Dyer,
Corinne Haioun,
Paul-Henri Roméo,
Philippe Gaulard, and
Karen Leroy
From the Département de Pathologie, the Service
d'Immunologie Biologique, and the Service d'Hématologie
Clinique, EA2348, AP-HP, Hôpital Henri Mondor, Créteil,
France; the Institute of Pathology, University of Ulm,
Germany; the Department of Pathology, University of
Leicester, United Kingdom; and the Département
d'Hématologie of Institut Cochin, Maternité Port-Royal,
Paris, France.
The molecular markers that distinguish primary mediastinal large
B-cell lymphoma (PMBL) from nonmediastinal diffuse large B-cell
lymphomas (NM-DLBLs) remain to be identified. Using cDNA representational difference analysis to compare PMBL and NM-DLBL transcripts, we isolated a cDNA fragment homologous to the
mouse B-cell interleukin 4 (IL-4)-inducible gene FIG1
(interleukin 4-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 up-regulated 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 reverse transcriptase-polymerase chain reaction (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
PMBLs and NM-DLBLs was statistically significant (Fisher test;
P = .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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