The c-Rel transcription factor and B-cell proliferation: a deal with the devil

Mutations in the NF-κB signaling pathway: implications for human disease

“…Consistent with a role for REL in human B-cell malignancy, v-Rel causes rapidly fatal lymphoid cell (primarily B-cell) lymphomas and leukemias in infected chickens, and likely serves as a model for how REL contributes to human B-cell malignancy. The REL protein is a 587 amino-acid polypeptide with an N-terminal RHD and a C-terminal domain that contains two transactivation subdomains (Gilmore et al, 2004).…”

“…REL gene amplifications have been detected at significant frequency in many types of human B-cell, and to a lesser extent T-cell, lymphoma (Table 2, see also Gilmore et al, 2004). These diseases include Hodgkin's lymphoma (HL) (B 50% REL amplifications) and non-Hodgkin's B-cell lymphomas (B10-20%).…”

“…However, it is important to note that in in vitro-transformed chicken spleen cells REL (and v-Rel) appear to be primarily cytoplasmic by immunofluorescence (Starczynowski et al, 2003), and yet the evidence is quite convincing that these oncogenic proteins are continually entering the nucleus to drive the gene transcription that causes transformation and immortalization of these cells (Gilmore, 1999;Gilmore et al, 2004). Thus, one cannot assume that cytoplasmic REL staining of lymphoma samples dictates the presence of only inactive REL complexes.…”

Mutation of an IKK phosphorylation site within the transactivation domain of REL in two patients with B-cell lymphoma enhances REL's in vitro transforming activity

“…c-rel knockout mice have normal numbers of mature B cells, but these cells do not proliferate in response to mitogenic stimulation (Ko¨nt-gen et al, 1995). Conversely, overexpression of chicken, mouse or human c-rel can transform chicken lymphoid cells in vitro and these cells can form lethal lymphomas in chickens (Gilmore et al, 2004). In addition, the REL locus is amplified in several types of human B-cell lymphoma, including diffuse large B-cell lymphomas (DLBCLs), follicular lymphomas (FLs) and primary mediastinal lymphomas (Gilmore et al, 2004).…”

“…Conversely, overexpression of chicken, mouse or human c-rel can transform chicken lymphoid cells in vitro and these cells can form lethal lymphomas in chickens (Gilmore et al, 2004). In addition, the REL locus is amplified in several types of human B-cell lymphoma, including diffuse large B-cell lymphomas (DLBCLs), follicular lymphomas (FLs) and primary mediastinal lymphomas (Gilmore et al, 2004). Moreover, REL mRNA is highly expressed in de novo DLBCLs, and this elevated expression correlates with increased expression of many REL target genes (Rhodes et al, 2005).…”