EXPRESSION OF THE PAX5 BSAP TRANSCRIPTION FACTOR IN HEMATOLOGICAL TUMOR-CELLS AND FURTHER MOLECULAR CHARACTERIZATION OF THE T(9-14)(G13-Q32) TRANSLOCATION IN B-CELL NON-HODGKINS-LYMPHOMA/

The PAX5 gene encodes the BSAP (B-cell-specific activator protein) whi ch is a key regulator of B-cell development and differentiation. A rec urring translocation t(9;14)(p13;q32) in non-Hodgkin's lymphoma moves the PAX5 on 9p13 within close proximity of the immunoglobulin heavy ch ain gene (IGH), KIS-1 cell line was established from a patient with di ffuse 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 h aematological tumour cell lines with other chromosome abnormalities in comparison with that of KIS-1. PAX5 mRNA and BSAP expression were det ected in all B-cell lines tested, and the high level in KIS-1 was conf irmed. However, a diffuse large B-cell lymphoma cell line and an acute B-lymphoid/myeloid leukaemia cell line expressed the PAX5/BSAP at lev els 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/BS AP activation in haematological tumour cells is not necessarily associ ated with t(9;14). Although binding sites for BSAP have been identifie d in the promoters of CD19, this study failed to find dear correlation between the level of PAX5/BSAP expression and that of CD19. In contra st to KIS-1 in which the E mu enhancer of IGH was juxtaposed to PAX5, cloning of t(9;14) from another case by long-distance PCR revealed tha t the PAX5 promoter was linked to a Cy constant region in divergent or ientation, suggesting that the mechanism of PAX5 activation through re combination with IGH varies among individual cases. Breakpoints on 9p1 3 of the two translocations were clustered upstream of PAX5, leaving t he PAX5 coding region intact.