Overexpression of a human Rel protein missing a C-terminal transactivation domain can also enhance the transformed state of the human B-lymphoma cell line BJAB.
We found an increase of genomic complexity with lymphoma progression from small to large cytology, and identified gains of prominent (proto) oncogenes such as REL, BCL11A, ETS1, PTPN1, PTEN and KRAS which were found exclusively in the large cell variants.
Reverse transcriptase-polymerase chain reaction analysis of mRNA from both primary lymphoma samples and several transformed tissue culture cell lines indicates that the RELDelta9 splice variant is preferentially expressed in lymphoma, suggesting that the REL transcript lacking exon 9 could serve as a marker for certain types of lymphoid tumors.
Gene expression analysis of angioimmunoblastic lymphoma indicates derivation from T follicular helper cells and vascular endothelial growth factor deregulation.
Although transcript levels were generally low and nuclear REL staining was weak in the lymphoma cell lines, these nevertheless exhibited high NF-kappaB activation.
Taken together, these results suggest the following: (1) that REL must activate transcription to transform cells in vitro; (2) that a reduced level of transactivation enhances the oncogenicity of REL; (3) that REL shuttles from the cytoplasm to the nucleus in transformed chicken spleen cells; and (4) that mutations in REL, in addition to amplifications, could activate its oncogenicity in human lymphomas.