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Blood, Vol. 94 No. 10 (November 15), 1999:
pp. 3567-3575
The MAL Gene Is Expressed in Primary Mediastinal Large B-Cell Lymphoma
Christiane Copie-Bergman,
Philippe Gaulard,
Leïla Maouche-Chrétien,
Josette Brière,
Corinne Haioun,
Miguel A. Alonso,
Paul-Henri Roméo, and
Karen Leroy
From the Département de Pathologie and EA 2348, the Service
d'Hématologie Clinique, AP-HP, Hôpital Henri Mondor,
Créteil, France; INSERM U 474, Créteil, France; the Service
d'Anatomie et de Cytologie Pathologiques, Hôpital Laennec,
Paris, France; the Centro de Biologia Molecular "Severo Ochoa,"
Universidad Autonoma de Madrid and Consejo Superior de Investigaciones
Cientificas, Cantoblanco, Madrid, Spain.
Primary mediastinal large B-cell lymphoma (PMBL) appears to be a
distinct clinicopathologic entity among diffuse large B-cell lymphomas
(DLBLs). To find molecular alterations associated with this disease, we
compared the mRNAs expressed in 3 PMBLs and 3 peripheral DLBLs by
differential display-reverse transcription (DDRT) and identified a mRNA
specifically expressed in PMBLs. Sequence analysis showed that this
mRNA is encoded by the MAL gene, the expression of which
was shown to be restricted to the T-cell lineage during hematopoiesis.
MAL gene expression was demonstrated by Northern blot and reverse
transcription-polymerase chain reaction (RT-PCR) in 8 of
12 PMBLs. However, there was little or no MAL gene expression in 8 peripheral DLBLs. Immunohistochemical analysis evidenced expression of
MAL protein in tumoral B cells restricted to the PMBL subtype. Finally,
Southern blot studies did not demonstrate rearrangement of the MAL
gene. Altogether, our results indicate that MAL expression is recurrent
in PMBLs, providing further evidence that PMBL represents a distinct
entity among DLBLs. Because MAL protein is located in
detergent-insoluble glycolipid-enriched membrane (GEM) domains involved
in lymphocyte signal transduction, abnormal expression of MAL protein
in the B-lymphoid lineage may have significant implications in PMBL lymphomagenesis.
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