Molecular mechanisms of transcriptional control of bcl-2 and c-myc in follicular and transformed lymphoma

A synergistic interaction of Bcl-2 and c-Myc plays a role in lymphomagenesi s in mice and in some patients as well, Progression of follicular lymphoma to a more aggressive lymphoma is seen in the majority of patients, and simi lar to 10% of the transformed lymphomas have a translocation of c-myc in ad dition to the translocation of bcl-2 found in the original follicular lymph oma. We investigated whether transcriptional deregulation of bcl-2 and c-my c could be examined in primary lymphoma cells by in vivo footprinting and l it vitro protein-DNA binding studies. A matched pair of follicular and tran sformed lymphoma samples was examined, The transformed lymphoma had acquire d a translocation of c-myc into the immunoglobulin heavy chain locus, High levels of bcl-2 expression mere observed in both the follicular and transfo rmed lymphomas, whereas the expression of c-myc was low in the follicular l ymphoma and increased in the transformed lymphoma, In vivo footprint analys is revealed that a CRE site and a Cdx site in the bcl-2 promoter were occup ied on the translocated alleles but not on the normal alleles in both the f ollicular and transformed lymphomas.; Two nuclear factor KB sites were occu pied on the translocated c-myc allele in the transformed lymphoma, Gel shif t analysis revealed that these proteins bound to their respective sites in the bcl-2 or c-myc promoter, There was no evidence that the presence of one of the translocations in the immunoglobulin heavy chain locus influenced t he expression of the other translacated gene.