STANDARD_NAME SHAFFER_IRF4_TARGETS_IN_MYELOMA_VS_MATURE_B_LYMPHOCYTE SYSTEMATIC_NAME M5784 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/SHAFFER_IRF4_TARGETS_IN_MYELOMA_VS_MATURE_B_LYMPHOCYTE NAMESPACE HUMAN_GENE_SYMBOL DESCRIPTION_BRIEF IRF4 [GeneID=3662] target genes up-regulated in primary myeloma vs. mature B lymphocytes. DESCRIPTION_FULL The transcription factor IRF4 (interferon regulatory factor 4) is required during an immune response for lymphocyte activation and the generation of immunoglobulin-secreting plasma cells. Multiple myeloma, a malignancy of plasma cells, has a complex molecular aetiology with several subgroups defined by gene expression profiling and recurrent chromosomal translocations. Moreover, the malignant clone can sustain multiple oncogenic lesions, accumulating genetic damage as the disease progresses. Current therapies for myeloma can extend survival but are not curative. Hence, new therapeutic strategies are needed that target molecular pathways shared by all subtypes of myeloma. Here we show, using a loss-of-function, RNA-interference-based genetic screen, that IRF4 inhibition is toxic to myeloma cell lines, regardless of transforming oncogenic mechanism. Gene expression profiling and genome-wide chromatin immunoprecipitation analysis uncovered an extensive network of IRF4 target genes and identified MYC as a direct target of IRF4 in activated B cells and myeloma. Unexpectedly, IRF4 was itself a direct target of MYC transactivation, generating an autoregulatory circuit in myeloma cells. Although IRF4 is not genetically altered in most myelomas, they are nonetheless addicted to an aberrant IRF4 regulatory network that fuses the gene expression programmes of normal plasma cells and activated B cells. PMID 18568025 GEOID GSE9031 AUTHORS Shaffer AL,Emre NC,Lamy L,Ngo VN,Wright G,Xiao W,Powell J,Dave S,Yu X,Zhao H,Zeng Y,Chen B,Epstein J,Staudt LM CONTRIBUTOR Jessica Robertson CONTRIBUTOR_ORG MSigDB Team EXACT_SOURCE Fig. 4bS: Primary myeloma > mature B cell FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS ACP1,AHCY,AMPD1,APOBEC3B,ATF3,ATF4,ATP5D,B3GNT1,BCKDHA,BCL2L2,BMI1,BMP6,BSPRY,C11orf24,CANX,CASP3,CAV1,CCL3,CCNC,CCPG1,CD38,CD97,CFLAR,CYCS,CYP51A1,DDIT3,DNAJB9,DNAJC10,DUSP5,EIF2S2,ELL1,F12,FHL1,FKBP11,GAA,GARS,GFPT1,GNG7,GRSF1,HDAC5,HMBS,HSP90AA1,HSP90B1,HSPB1,ISG20,ITGA4,KRAS,LDHA,LDLR,LDLRAP1,MAN2A1,MARS,MPZL1,MXI1,MYC,NDRG1,NFIL3,NP,NR4A1,P4HA1,PABPC4,PAICS,PAM,PBEF1,PDIA4,PDK1,PGK1,PIM2,PIP5K1B,PPP1R2,PPP2R5C,PRDM1,SCC-112,SLAMF7,SLC31A1,SLC37A4,SLC38A2,SLC3A2,SORT1,SPATS2,SSR1,SUB1,SUMO1,TIMP2,TLOC1,TM9SF4,TNFAIP3,TNFRSF17,TRAM1,TUFT1,TXNDC5,UAP1,UBE2B,UBE2H,UBE2J1,UCK2,VDAC1,XPOT,YARS,YES1,ZFP36 GENE_SYMBOLS ACP1,AHCY,AMPD1,APOBEC3B,ATF3,ATF4,ATP5F1D,B3GNT2,BCKDHA,BCL2L2,BMI1,BMP6,BSPRY,C11orf24,CANX,CASP3,CAV1,CCL3,CCNC,CCPG1,CD38,ADGRE5,CFLAR,CYCS,CYP51A1,DDIT3,DNAJB9,DNAJC10,DUSP5,EIF2S2,ELL,F12,FHL1,FKBP11,GAA,GARS1,GFPT1,GNG7,GRSF1,HDAC5,HMBS,HSP90AA1,HSP90B1,HSPB1,ISG20,ITGA4,KRAS,LDHA,LDLR,LDLRAP1,MAN2A1,MARS1,MPZL1,MXI1,MYC,NDRG1,NFIL3,PNP,NR4A1,P4HA1,PABPC4,PAICS,PAM,NAMPT,PDIA4,PDK1,PGK1,PIM2,PIP5K1B,PPP1R2,PPP2R5C,PRDM1,PDS5A,SLAMF7,SLC31A1,SLC37A4,SLC38A2,SLC3A2,SORT1,SPATS2,SSR1,SUB1,SUMO1,TIMP2,SEC62,TM9SF4,TNFAIP3,TNFRSF17,TRAM1,TUFT1,TXNDC5,UAP1,UBE2B,UBE2H,UBE2J1,UCK2,VDAC1,XPOT,YARS1,YES1,ZFP36 FOUNDER_NAMES