Fig. 2: Aberrant NF-κB signalling targets dormant myeloma enhancers.

a Western blot for key non-canonical NF-κB pathway members - NFKB2 (p100/p52), NIK, TRAF3 and RelB across constitutively activated mutant MMCLs (MM1.S, RPMI8226, U266, LP1, KMS-11, MM1.144, ANBL6, JJN3, L363) resulting from TRAF3 and NIK mutations as well as non-mutant MMCLs (XG7, H929, MOLP8), n = 2. b Radar plot showing distribution of detected p52 binding sites at genomic features. c Euler diagram illustrating the overlap in p52 binding sites (n = 6367) at intergenic or intronic H3K27ac peaks (peaks in at least two replicates) detected across all six MMCLs with total sites in each cell line indicated. d Proposed mechanism for the activation of dormant enhancers during hyperactive NF-κB signalling in NF-κB mutant myeloma cells. e Classification of patient MM and PB samples (blue text) using an NF-κB index based on the geometric mean of the expression for 11 NF-κB signature genes (as performed for the MMRF data). RNA-seq datasets are matched with epigenomic data from two main studies²⁰ and¹⁹ annotated in brown and black text respectively. f H3K27ac signal (Z-score of normalised rLog counts) at intronic and intergenic p52 binding sites across multiple myeloma patients contrasting high and low NF-κB index samples. Loci are annotated with STABILO. g Cancer related biological processes found to be significantly associated with genes in proximity to the p52 binding sites enriched in H3K27 acetylation in NF-κB+ patients relative to NF-κB- (GREAT analysis; HyperFdrQ ≤ 0.1).