The MAL gene is expressed in primary mediastinal large B-cell lymphoma

Primary mediastinal large B-cell lymphoma (PMBL) appears to be a distinct c linicopathologic entity among diffuse large B-cell lymphomas (DLBLs). To fi nd molecular alterations associated with this disease, we compared the mRNA s expressed in 3 PMBLs and 3 peripheral DLBLs by differential display-rever se transcription (DDRT) and identified a mRNA specifically expressed in PMB Ls. 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 durin g 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 NIAL gene expression in 8 peripheral DLBLs. Immunohistochemical analysis evidenced expression of MAL protein in tumora l B cells restricted to the PMBL subtype. Finally, Southern blot studies di d not demonstrate rearrangement of the MAL gene. Altogether, our results in dicate that MAL expression is recurrent in PMBLs, providing further evidenc e that PMBL represents a distinct entity among DLBLs. Because MAL protein i s located in detergent-insoluble glycolipid-enriched membrane (GEM) domains involved in lymphocyte signal transduction, abnormal expression of MAL pro tein in the B-lymphoid lineage may have significant implications in PMBL ly mphomagenesis. (C) 1999 by The American Society of Hematology.