The c-MYC/IGH fusion gene of DLCL is identical to that of the sporadic type of BL (sBL). DLCL with c-MYC/IGH shares clinical features with sBL but is characterized further by an older age distribution.

Anaplastic large cell lymphoma (ALCL) with t(2;5)(p23;q35) and Hodgkin disease (HD) share many cellular features, including expression of CD30. We compared gene expression profiles of 4 ALCL (Karpas 299, SU-DHL-1, DEL, SR-786) and 3 HD cell lines and found that BCL3, which encodes a nuclear protein belonging to the IB family of inhibitors of nuclear factor-B (NF-B) transcriptional factors, was expressed at higher levels in ALCL than HD. Northern and Western blotting analyses confirmed the high-level expression of BCL3 in ALCL at both mRNA and protein levels. We established a real-time reverse transcriptase-mediated polymerase chain reaction assay to measure the BCL3 mRNA level and found a predominant level of BCL3 expression in t(2;5) ؉ ALCL; the levels of cell lines and clinical materials were comparable to or higher than that of a B-cell chronic lymphocytic leukemia carrying t(14;19)(q32;q13). Southern blotting and fluorescence in situ hybridization disclosed that the BCL3 gene copies were amplified in SU-DHL-1, whereas Karpas 299 carried 4 BCL3 gene loci. The BCL3 gene contains 2 cytosineguanine dinucleotide (CpG) islands, and the intragenic 3 CpG was entirely demethylated in SU-DHL-1 and DEL. In contrast to HD, in which NF-B was constitutively activated, ALCL cells consistently showed (p50) 2 homodimer binding activity on electrophoretic mobility shift assay. It is suggested that the high-level nuclear Bcl-3 sequestrates the (p50) 2 homodimer to the nucleus, which may account for the contradictory effect of CD30 stimulation on ALCL and HD. We propose that BCL3 is overexpressed by genetic and epigenetic modifications, potentially contributing to the development of t(2;5) ؉ ALCL. (Blood.

Summary. The PAX5 gene encodes the BSAP (B-cell-specific activator protein) which is a key regulator of B-cell development and differentiation. A recurring translocation t(9;14)(p13;q32) in non-Hodgkin's lymphoma moves the PAX5 on 9p13 within close proximity of the immunoglobulin heavy chain gene (IGH). KIS-1 cell line was established from a patient with diffuse large cell lymphoma of B-cell type carrying t(9;14). We analysed PAX5/BSAP expression by Northern and Western blotting in a panel of haematological tumour cell lines with other chromosome abnormalities in comparison with that of KIS-1. PAX5 mRNA and BSAP expression were detected in all B-cell lines tested, and the high level in KIS-1 was confirmed. However, a diffuse large B-cell lymphoma cell line and an acute B-lymphoid/myeloid leukaemia cell line expressed the PAX5/BSAP at levels comparable with KIS-1. PAX5 transcripts were readily detectable in clinical materials with a wide variety of B-cell neoplasms by reverse transcriptase-mediated polymerase chain reaction (PCR). Thus, PAX5/BSAP activation in haematological tumour cells is not necessarily associated with t(9;14). Although binding sites for BSAP have been identified in the promoters of CD19, this study failed to find clear correlation between the level of PAX5/BSAP expression and that of CD19. In contrast to KIS-1 in which the Em enhancer of IGH was juxtaposed to PAX5, cloning of t(9;14) from another case by long-distance PCR revealed that the PAX5 promoter was linked to a Cg constant region in divergent orientation, suggesting that the mechanism of PAX5 activation through recombination with IGH varies among individual cases. Breakpoints on 9p13 of the two translocations were clustered upstream of PAX5, leaving the PAX5 coding region intact.

BCL6 translocation aecting the chromosomal band 3q27 can involve a number of non-immunoglobulin (non-IG) gene loci as partners. We report here that the gene for interleukin-21 receptor (IL-21R) is the partner of BCL6 in t(3;16)(q27;p11) translocation. The two breakpoints on 16p11 of a lymphoma cell line YM and case no. 1012 with diuse large B-cell lymphoma, both of which carried t(3;16), were localized within the *27-kb intron 1 of IL-21R. As a result of t(3;16), the promoter region of IL-21R was substituted for the regulatory sequences of BCL6 in the same transcriptional orientation. Reverse transcriptase-mediated polymerase chain reaction revealed chimeric mRNA consisting of two noncoding exons 1a/1b of IL-21R and coding exons of BCL6 in both lymphoma cells. Fluorescence in situ chromosomal hybridization of YM metaphase cells revealed fusion signals that contained both the BCL6 and IL-21R sequences on the der(3)t(3;16) chromosome. IL-21R was actively transcribed in YM cells, while BCL6 that was under the control of the IL-21R promoter was only moderately expressed at the mRNA and protein level. We constructed expression plasmid of BCL6 that followed the promoter sequences of IL-21R. COS-7 cells transiently transfected with the plasmid expressed high level Bcl-6 protein and displayed nuclear staining with a characteristic punctate pattern by immuno¯uorescence, indicating that expression of BCL6 can be enhanced by t(3;16). This study added to the list of non-IG partners of BCL6 translocations a new class of gene, i.e. cytokine receptor gene, the expression of which is closely associated with lymphoid cells.