Atlas of Genetics and Cytogenetics in Oncology and Haematology


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IRF4 (interferon regulatory factor 4)

Identity

Other namesIRF-4
LSIRF
MUM1
NF-EM5
HGNC (Hugo) IRF4
LocusID (NCBI) 3662
Location 6p25.3
Location_base_pair Starts at 391739 and ends at 411443 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order IRF4 is located on chromosome 6 at the telomeric extremity of the short arm, and lies between the DUSP22 (dual specificity phosphatase 22) and EXOC2 (exocyst complex component 2) genes.
Note IRF4 belongs to the IRF (interferon regulatory factors) family of transcription factors and is a critical transcriptional regulator of immune system development and function.

DNA/RNA

 
Description Gene of 19,4 kb with 9 exons and 8 introns.
Exon 1, the 5' part of exon 2 and the 3' part of exon 9 are non coding.
Transcription Length of the transcript is 5314 bp.
Coding sequence: CDS 114-1469.
mRNA is expressed at high levels in lymphoid tissues, in skin and in tonsils.

Protein

Description Protein length: 451 amino acids.
Calculated molecular weight of 51,8 kDa.
Expression IRF4 protein is expressed predominantly in blood cells. However, its expression can also be detected in adipocytes and melanocytes. In blood cells, expression of IRF4 can be detected in T, B, DC and macrophages. Expression of IRF4 in T and B cells is strongly induced by antigen receptor signaling.
Localisation Nucleus.
Function In the immune system, IRF4 is critical for development and maturation of multiple lineages of blood cells. In T cells development, IRF4 is essential for the differentiation of Th1, Th2, Th9, Th17 and T reg subsets. In B lymphocytes, IRF4 promotes light chain rearrangement and transcription and is critical for B cell development at the pre-B stage. IRF4 antagonizes Notch signaling and limits the size of marginal zone B cells (Simonetti et al., 2013). In addition, IRF4 is essential for class-switching and plasma cell differentiation. In B cells, IRF4 interacts with Ets family of trancription factor (PU.1/spi-B) through EICE site whereas in T cells, IRF4 interacts with AP-1 family of trancription factor (BATF) through AICE site. Also, IRF4 is required for the differentiation of dendritic cells (DCs), particularly the CD11b(+) subset (Schlitzer et al., 2013). In macrophages, IRF4 promotes the differentiation and polarisation to the M2 subtype also known as the tumor associated macrophages.
Recent studies have identified a role of IRF4 in adipocyte biology. IRF4 has been shown to regulate enzymes required for lipolysis in adipocytes. Therefore, an adipocyte specific deletion of IRF4 causes enhanced lipid synthesis, dysregulated lipid homeostasis eventually leading to obesity.
Interestingly, in melanocytes IRF4 was recently identified to cooperate with another transcription factor, MITF to positively regulate the expression of tyrosinase gene required for melanin synthesis. Additionally, the SNPs in the IRF4 gene locus have been identified as risk alleles for developing melanoma.
Homology Among IRF family members, IRF4 is highly homologous to IRF8.

Mutations

Germinal SNPs in the IRF4 gene locus have been identified in patients with chronic lymphocytic leukemia and melanoma.
Somatic Somatic mutations in DNA binding domain of IRF4 have been identified in a small subset (1,5%) of chronic lymphocytic leukemia (CLL) patients.

Implicated in

Entity Multiple myeloma (MM)
Disease Multiple myeloma (MM) is a plasma cell derived malignancy with a particularly aggressive clinical course. IRF4 is obligatory required for the terminal differetiation of mature B cells to plasma cells and has been shown to play a central role in the pathogenesis of MM. IRF4 is recurrently translocated and juxtaposed to the IgH promoter t(6;14)(p25;q32) in a significant proportion (~21%) of MM cases. More commonly, IRF4 have been shown to be overexpressed without genetic alterations in majority of MM cases and MM cells are particularly sensitive to the down-regulation of IRF4.
Cytogenetics t(6;14)(p25;q32) --> IRF4 - IgH.
Hybrid/Mutated Gene The translocation juxtaposes the IgH locus to the IRF4 gene.
Oncogenesis The precise mechanism for pathogenesis of MM in presence of high levels of IRF4 is mediated by an autoregulatory loop established between IRF4 and c-myc in MM cells. Recently, IRF4 has been shown to regulate caspase-10 leading to disruption of normal autophagy mechanisms in MM cells thereby, causing prolonged survival of these cells.
  
Entity Chronic lymphocytic leukemia (CLL)
Disease CLL is the most common adult leukemia in the western countries. It is a heterogeneous B-cell malignancy marked by progressive accumulation of CD5 positive mature B lymphocytes. A Genome Wide Association Study (GWAS) recently identified SNPs in the 3' UTR of IRF4 gene locus in patients with CLL. The individuals carrying the risk alleles harboring the SNPs have lower levels of IRF4 and poorer outcomes compared to individuals carrying the non-risk allele. Another study identified mutations in the DNA binding domain of IRF4 in a small subset (1,5%) of CLL cases. More recently, using two distinct murine genetic models, it has been shown that low levels of IRF4 are causally related to the development of CLL.
Prognosis CLL patients with low levels of IRF4 have aggressive disease course and poor prognosis.
Cytogenetics Although reciprocal translocations are extremely rare in CLL, a translocation disrupting IRF4 gene locus t(1;6)(p35.3;p25.2) was identified in a small subset of CLL patients with aggressive disease.
Hybrid/Mutated Gene Mutations in the DNA binding domain of IRF4 with a yet undefined function in B cells were identified in a small subset of CLL cases.
Oncogenesis The precise mechanism for oncogenesis of CLL in presence of low levels of IRF4 is not yet known.
  
Entity Diffused large B cell lymphoma (DLBCL)
Disease Diffuse large B cell lymphoma represents a heterogeneous malignancy that arises spontaneously or develop from pre-existing leukemia. On the basis of gene expression profiling DLBCL is divided into three distinct subtypes namely the germinal center subtype (GCB), the activated B cell subtype (ABC) and the mediastinal subtype. The three subtypes presumably arise from three distinct B cell subtypes. IRF4 is primarily overexpressed in the ABC type of DLBCL while GCB subtype is marked by lower expression of IRF4.
Prognosis IRF4 is overexpressed in the ABC type DLBCL which is most aggressive form of DLBCL and have poorer patient outcomes compared to other subtypes.
Cytogenetics IRF4 is overexpressed in a small group of patients with a reciprocal translocation between IgG locus and the IRF4 t(1;6)(p35.3;p25.2). The patients carrying the translocation primarily belong to GCB or follicular lymphoma grade 3 type is associated with favorable patient outcomes.
Oncogenesis IRF4 induces the expression of transcription factor Blimp-1 and directly suppresses the expression of Bcl-6 to allow terminal differentiation of activated B cells to plasma cells. However, this molecular network is short circuited in ABC DLBCL by recurrent mutational inactivation of Blimp-1. Additionally, mutations located in the promoter region of Bcl-6 that disrupt the IRF4 binding sites and leads to enhanced expression of Bcl-6 were identified in a small group of patients. These genetic events disrupt the molecular network required for plasma cell differentiation. However, the precise functional role of IRF4 in pathogenesis of ABC type DLBCL is not well defined.
  
Entity Hodgkins lymphoma (HL)
Disease Hodgkins lymphoma (HL) is an enigmatic B cell malignancy that is characterized by lack of expression of several B cell markers. The Hodgkin and Reed Sternberg (HRS) cells present in HL cases are presumably derived from germinal center B cells. IRF4 is overexpressed in majority of classical HL cases and is shown to mediate the survival of these cells. Paradoxically, the SNPs in IRF4 linked to its lower expression levels and associated with the development of CLL are also shown to be linked to the risk of developing HL.
Oncogenesis Whether the overexpression of IRF4 in HRS cells of HL is causal is unclear. However, some studies have linked the survival and proliferation of HRS cells to the expression of IRF4.
  
Entity Primary cutaneous anaplastic large cell lymphoma (C-ALCL)
Disease Primary cutaneous anaplastic large cell lymphoma (C-ALCL) is a T cell lymphoma with an indolent disease course and presence of tumor lesions in the skin. The lesions in C-ALCL almost never spread extra-cutaneously and often regress spontaneously. IRF4 is overexpressed in C-ALCL but not in the more aggressive form of the disease known as peripheral T cell lymphoma not otherwise specified (PTCL-NOS). The overexpression of IRF4 in some cases is associated with a recurrent translocations a subset of them placing the IRF4 gene next to the T cell receptor alpha (TCRA) promoter t(6;14)(p25;q11.2). Other translocations identified do not involve TCRA.
Cytogenetics IRF4 is translocated primarily in the C-ALCL however the precise breakpoints are not defined. In a small subset of the cases with translocations IRF4 is juxtaposed to the TCRA locus t(6;14)(p25;q11.2).
  
Entity B cell acute lymphoblastic leukemia (B-ALL)
Disease B cell acute lymphoblastic leukemia (B-ALL) is a B cell malignancy derived from early B cells. IRF4 is shown to play a tumor suppressive role in B-ALL. IRF4 is shown to suppress the oncogenesis of both BCR-ABL and c-myc induced B-ALL.
Oncogenesis IRF4 inhibits B-ALL by regulating the expression of negative regulators of cell cycle p27.
  
Entity Chronic myeloid leukemia (CML)
Disease Chronic myeloid leukemia (CML) is a myeloproliferative disorder marked by clonal expansion of granulocytes. It is associated with a hallmark translocation and presence of a fusion BCR-ABL protein in majority of patients. IRF4 is shown to be underexpressed in CML patients along with its highly homologous family member IRF8. However the functional role of IRF4 in CML is not well characterized.
  
Entity Virus implicated malignancies
Disease Viruses like Epstein Barr virus (EBV), human T cell leukemia virus-1 (HTLV1) and Kaposi Sarcoma associated herpes virus (KSHV/HHV-8) are implicated in B cell malignancies, adult T cell leukemia (ATL) and primary effusion lymphoma (PEL) respectively. The proteins encoded by these viruses, directly or indirectly activate NF-kB signaling which in turn activates the expression of IRF4. As a result IRF4 is overexpressed in these virus implicated malignancies. The knockdown of IRF4 in EBV transformed B cells lead to down-regulation of genes involved in cellular proliferation. The role of IRF4 in HTLV-1 induced ATL is not clear however few reports indicate its involvement in regulation of cell cycle associated genes. The role of IRF4 in KSHV induced kaposi's sarcoma and PEL is ambiguous. KSHV encodes viral homologs of cellular IRFs called vIRFs. The vIRF4 is shown to inhibit the function of cellular IRF4 leading to induction of lytic cycle for KSHV replication.
Oncogenesis The role of IRF4 in these viral implicated malignancies is still unclear. However, the activation status of NF-kB by these viruses invariably co-relates with IRF4 expression in these cells.
  
Entity Skin cancer
Disease Skin cancer is associated with malignant or non-malignant lesions on the skin. Based on the cell of origin, skin cancer can be divided into three types: basal cell carcinoma, squamous cell carcinoma and melanoma. The differential skin pigmentation induced by melanin production alters the risk for skin cancer. Particularly individuals with light skin tones and hence low melanin secretion are more predisposed to developing skin cancer. Until recently there were no known reports for a role of IRF4 in melanocytes. However recently, SNPs identified in the IRF4 gene locus have been shown to be associated with skin pigmentation and the risk for developing skin cancer. The SNP identified in the screen map to a putative enhancer region in the IRF4 gene locus.
Oncogenesis Recently, the SNP identified in IRF4 locus were demonstrated to decrease IRF4 expression by disruption of specific transcription factor binding sites. Additionally, IRF4 corroborates with micropthalmia associated transcription factor (MITF) to regulate the expression of enzyme tyrosinase responsible for melanin production. These studies point towards a critical role for IRF4 in melanocyte biology and also its association with skin cancer.
  

Other Leukemias implicated (Data extracted from papers in the Atlas)

Leukemias 11q23ChildAMLID1615 11q23ID1030 11q23secondLeukID1131 t1119ELLID1029

External links

Nomenclature
HGNC (Hugo)IRF4   6119
Cards
AtlasIRF4ID231ch6p25
Entrez_Gene (NCBI)IRF4  3662  interferon regulatory factor 4
GeneCards (Weizmann)IRF4
Ensembl (Hinxton)ENSG00000137265 [Gene_View]  chr6:391739-411443 [Contig_View]  IRF4 [Vega]
ICGC DataPortalENSG00000137265
cBioPortalIRF4
AceView (NCBI)IRF4
Genatlas (Paris)IRF4
WikiGenes3662
SOURCE (Princeton)NM_001195286 NM_002460
Genomic and cartography
GoldenPath (UCSC)IRF4  -  6p25.3   chr6:391739-411443 +  6p25-p23   [Description]    (hg19-Feb_2009)
EnsemblIRF4 - 6p25-p23 [CytoView]
Mapping of homologs : NCBIIRF4 [Mapview]
OMIM254500   601900   
Gene and transcription
Genbank (Entrez)AK130762 AK310149 AW197089 BC015752 BG230623
RefSeq transcript (Entrez)NM_001195286 NM_002460
RefSeq genomic (Entrez)AC_000138 NC_000006 NC_018917 NG_027728 NT_007592 NW_001838972 NW_004929326
Consensus coding sequences : CCDS (NCBI)IRF4
Cluster EST : UnigeneHs.401013 [ NCBI ]
CGAP (NCI)Hs.401013
Alternative Splicing : Fast-db (Paris)GSHG0025358
Alternative Splicing GalleryENSG00000137265
Gene ExpressionIRF4 [ NCBI-GEO ]     IRF4 [ SEEK ]   IRF4 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ15306 (Uniprot)
NextProtQ15306  [Medical]
With graphics : InterProQ15306
Splice isoforms : SwissVarQ15306 (Swissvar)
Domaine pattern : Prosite (Expaxy)IRF_1 (PS00601)    IRF_2 (PS51507)   
Domains : Interpro (EBI)Interferon_reg_fac_CS [organisation]   Interferon_reg_fact_DNA-bd_dom [organisation]   Interferon_reg_factor-3 [organisation]   SMAD_dom-like [organisation]   SMAD_FHA_domain [organisation]   WHTH_DNA-bd_dom [organisation]  
Related proteins : CluSTrQ15306
Domain families : Pfam (Sanger)IRF (PF00605)    IRF-3 (PF10401)   
Domain families : Pfam (NCBI)pfam00605    pfam10401   
Domain families : Smart (EMBL)IRF (SM00348)  
DMDM Disease mutations3662
Blocks (Seattle)Q15306
PDB (SRS)2DLL   
PDB (PDBSum)2DLL   
PDB (IMB)2DLL   
PDB (RSDB)2DLL   
Human Protein AtlasENSG00000137265 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasQ15306
HPRD03543
IPIIPI00289982   IPI00215970   IPI00981040   
Protein Interaction databases
DIP (DOE-UCLA)Q15306
IntAct (EBI)Q15306
FunCoupENSG00000137265
BioGRIDIRF4
InParanoidQ15306
Interologous Interaction database Q15306
IntegromeDBIRF4
STRING (EMBL)IRF4
Ontologies - Pathways
Ontology : AmiGOnuclear nucleosome  regulatory region DNA binding  sequence-specific DNA binding transcription factor activity  sequence-specific DNA binding transcription factor activity  protein binding  nucleus  cytosol  transcription, DNA-templated  transcription factor binding  membrane  protein-lysine N-methyltransferase activity  peptidyl-lysine methylation  cytokine-mediated signaling pathway  negative regulation of toll-like receptor signaling pathway  T cell activation  defense response to protozoan  myeloid dendritic cell differentiation  positive regulation of DNA binding  sequence-specific DNA binding  histone H3 acetylation  histone H4 acetylation  positive regulation of interleukin-10 biosynthetic process  positive regulation of interleukin-2 biosynthetic process  positive regulation of interleukin-13 biosynthetic process  positive regulation of interleukin-4 biosynthetic process  regulation of T-helper cell differentiation  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  interferon-gamma-mediated signaling pathway  type I interferon signaling pathway  T-helper 17 cell lineage commitment  
Ontology : EGO-EBInuclear nucleosome  regulatory region DNA binding  sequence-specific DNA binding transcription factor activity  sequence-specific DNA binding transcription factor activity  protein binding  nucleus  cytosol  transcription, DNA-templated  transcription factor binding  membrane  protein-lysine N-methyltransferase activity  peptidyl-lysine methylation  cytokine-mediated signaling pathway  negative regulation of toll-like receptor signaling pathway  T cell activation  defense response to protozoan  myeloid dendritic cell differentiation  positive regulation of DNA binding  sequence-specific DNA binding  histone H3 acetylation  histone H4 acetylation  positive regulation of interleukin-10 biosynthetic process  positive regulation of interleukin-2 biosynthetic process  positive regulation of interleukin-13 biosynthetic process  positive regulation of interleukin-4 biosynthetic process  regulation of T-helper cell differentiation  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  interferon-gamma-mediated signaling pathway  type I interferon signaling pathway  T-helper 17 cell lineage commitment  
Pathways : BIOCARTAThe information-processing pathway at the IFN-beta enhancer [Genes]   
Protein Interaction DatabaseIRF4
Wikipedia pathwaysIRF4
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)IRF4
snp3D : Map Gene to Disease3662
SNP (GeneSNP Utah)IRF4
SNP : HGBaseIRF4
Genetic variants : HAPMAPIRF4
Exome VariantIRF4
1000_GenomesIRF4 
ICGC programENSG00000137265 
Cancer Gene: CensusIRF4 
Somatic Mutations in Cancer : COSMICIRF4 
CONAN: Copy Number AnalysisIRF4 
Mutations and Diseases : HGMDIRF4
Mutations and Diseases : intOGenIRF4
Genomic VariantsIRF4  IRF4 [DGVbeta]
dbVarIRF4
ClinVarIRF4
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM254500    601900   
MedgenIRF4
GENETestsIRF4
Disease Genetic AssociationIRF4
Huge Navigator IRF4 [HugePedia]  IRF4 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneIRF4
Homology/Alignments : Family Browser (UCSC)IRF4
Phylogenetic Trees/Animal Genes : TreeFamIRF4
Chemical/Protein Interactions : CTD3662
Chemical/Pharm GKB GenePA29918
Clinical trialIRF4
Cancer Resource (Charite)ENSG00000137265
Other databases
Probes
Litterature
PubMed116 Pubmed reference(s) in Entrez
CoreMineIRF4
iHOPIRF4
OncoSearchIRF4

Bibliography

Cloning of human lymphocyte-specific interferon regulatory factor (hLSIRF/hIRF4) and mapping of the gene to 6p23-p25.
Grossman A, Mittrucker HW, Nicholl J, Suzuki A, Chung S, Antonio L, Suggs S, Sutherland GR, Siderovski DP, Mak TW.
Genomics. 1996 Oct 15;37(2):229-33.
PMID 8921401
 
Deregulation of MUM1/IRF4 by chromosomal translocation in multiple myeloma.
Iida S, Rao PH, Butler M, Corradini P, Boccadoro M, Klein B, Chaganti RS, Dalla-Favera R.
Nat Genet. 1997 Oct;17(2):226-30.
PMID 9326949
 
Requirement for the transcription factor LSIRF/IRF4 for mature B and T lymphocyte function.
Mittrucker HW, Matsuyama T, Grossman A, Kundig TM, Potter J, Shahinian A, Wakeham A, Patterson B, Ohashi PS, Mak TW.
Science. 1997 Jan 24;275(5299):540-3.
PMID 8999800
 
MUM1/IRF4 expression as a frequent event in mature lymphoid malignancies.
Tsuboi K, Iida S, Inagaki H, Kato M, Hayami Y, Hanamura I, Miura K, Harada S, Kikuchi M, Komatsu H, Banno S, Wakita A, Nakamura S, Eimoto T, Ueda R.
Leukemia. 2000 Mar;14(3):449-56.
PMID 10720141
 
Expression of MUM1/IRF4 correlates with clinical outcome in patients with B-cell chronic lymphocytic leukemia.
Chang CC, Lorek J, Sabath DE, Li Y, Chitambar CR, Logan B, Kampalath B, Cleveland RP.
Blood. 2002 Dec 15;100(13):4671-5. Epub 2002 Aug 1.
PMID 12393648
 
Proteins encoded by genes involved in chromosomal alterations in lymphoma and leukemia: clinical value of their detection by immunocytochemistry.
Falini B, Mason DY.
Blood. 2002 Jan 15;99(2):409-26. Review
PMID 11781220
 
MUM1/IRF4 expression is an unfavorable prognostic factor in B-cell chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).
Ito M, Iida S, Inagaki H, Tsuboi K, Komatsu H, Yamaguchi M, Nakamura N, Suzuki R, Seto M, Nakamura S, Morishima Y, Ueda R.
Jpn J Cancer Res. 2002 Jun;93(6):685-94.
PMID 12079517
 
Repression of IRF-4 target genes in human T cell leukemia virus-1 infection.
Mamane Y, Grandvaux N, Hernandez E, Sharma S, Innocente SA, Lee JM, Azimi N, Lin R, Hiscott J.
Oncogene. 2002 Oct 3;21(44):6751-65.
PMID 12360402
 
Identification of a novel GC-rich binding protein that binds to an indispensable element for constitutive IRF-4 promoter activity in B cells.
Nishiya N, Yamamoto K, Imaizumi Y, Kohno T, Matsuyama T.
Mol Immunol. 2004 Jul;41(9):855-61.
PMID 15261457
 
Interferon regulatory factor 4 negatively regulates the production of proinflammatory cytokines by macrophages in response to LPS.
Honma K, Udono H, Kohno T, Yamamoto K, Ogawa A, Takemori T, Kumatori A, Suzuki S, Matsuyama T, Yui K.
Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):16001-6. Epub 2005 Oct 21.
PMID 16243976
 
Negative regulation of Toll-like-receptor signaling by IRF-4.
Negishi H, Ohba Y, Yanai H, Takaoka A, Honma K, Yui K, Matsuyama T, Taniguchi T, Honda K.
Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):15989-94. Epub 2005 Oct 19.
PMID 16236719
 
Down-regulation of interferon regulatory factor 4 gene expression in leukemic cells due to hypermethylation of CpG motifs in the promoter region.
Ortmann CA, Burchert A, Holzle K, Nitsche A, Wittig B, Neubauer A, Schmidt M.
Nucleic Acids Res. 2005 Dec 7;33(21):6895-905. Print 2005.
PMID 16396836
 
IRF-4 functions as a tumor suppressor in early B-cell development.
Acquaviva J, Chen X, Ren R.
Blood. 2008 Nov 1;112(9):3798-806. doi: 10.1182/blood-2007-10-117838. Epub 2008 Aug 19.
PMID 18713947
 
A genome-wide association study identifies six susceptibility loci for chronic lymphocytic leukemia.
Di Bernardo MC, Crowther-Swanepoel D, Broderick P, Webb E, Sellick G, Wild R, Sullivan K, Vijayakrishnan J, Wang Y, Pittman AM, Sunter NJ, Hall AG, Dyer MJ, Matutes E, Dearden C, Mainou-Fowler T, Jackson GH, Summerfield G, Harris RJ, Pettitt AR, Hillmen P, Allsup DJ, Bailey JR, Pratt G, Pepper C, Fegan C, Allan JM, Catovsky D, Houlston RS.
Nat Genet. 2008 Oct;40(10):1204-10. doi: 10.1038/ng.219. Epub 2008 Aug 31.
PMID 18758461
 
Interferon regulatory factor 4 and 8 in B-cell development.
Lu R.
Trends Immunol. 2008 Oct;29(10):487-92. doi: 10.1016/j.it.2008.07.006. Epub 2008 Sep 3. (REVIEW)
PMID 18775669
 
IRF4 addiction in multiple myeloma.
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.
Nature. 2008 Jul 10;454(7201):226-31. Epub 2008 Jun 22.
PMID 18568025
 
Recurrent translocations involving the IRF4 oncogene locus in peripheral T-cell lymphomas.
Feldman AL, Law M, Remstein ED, Macon WR, Erickson LA, Grogg KL, Kurtin PJ, Dogan A.
Leukemia. 2009 Mar;23(3):574-80. doi: 10.1038/leu.2008.320. Epub 2008 Nov 6.
PMID 18987657
 
IRF4: Immunity. Malignancy! Therapy?
Shaffer AL, Emre NC, Romesser PB, Staudt LM.
Clin Cancer Res. 2009 May 1;15(9):2954-61. doi: 10.1158/1078-0432.CCR-08-1845. Epub 2009 Apr 21. (REVIEW)
PMID 19383829
 
Regulatory T-cell suppressor program co-opts transcription factor IRF4 to control T(H)2 responses.
Zheng Y, Chaudhry A, Kas A, deRoos P, Kim JM, Chu TT, Corcoran L, Treuting P, Klein U, Rudensky AY.
Nature. 2009 Mar 19;458(7236):351-6. doi: 10.1038/nature07674. Epub 2009 Feb 1.
PMID 19182775
 
The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection.
Satoh T, Takeuchi O, Vandenbon A, Yasuda K, Tanaka Y, Kumagai Y, Miyake T, Matsushita K, Okazaki T, Saitoh T, Honma K, Matsuyama T, Yui K, Tsujimura T, Standley DM, Nakanishi K, Nakai K, Akira S.
Nat Immunol. 2010 Oct;11(10):936-44. doi: 10.1038/ni.1920. Epub 2010 Aug 22.
PMID 20729857
 
Transcriptional control of adipose lipid handling by IRF4.
Eguchi J, Wang X, Yu S, Kershaw EE, Chiu PC, Dushay J, Estall JL, Klein U, Maratos-Flier E, Rosen ED.
Cell Metab. 2011 Mar 2;13(3):249-59. doi: 10.1016/j.cmet.2011.02.005.
PMID 21356515
 
A genomic regulatory element that directs assembly and function of immune-specific AP-1-IRF complexes.
Glasmacher E, Agrawal S, Chang AB, Murphy TL, Zeng W, Vander Lugt B, Khan AA, Ciofani M, Spooner CJ, Rutz S, Hackney J, Nurieva R, Escalante CR, Ouyang W, Littman DR, Murphy KM, Singh H.
Science. 2012 Nov 16;338(6109):975-80. doi: 10.1126/science.1228309. Epub 2012 Sep 13.
PMID 22983707
 
Exploiting synthetic lethality for the therapy of ABC diffuse large B cell lymphoma.
Yang Y, Shaffer AL 3rd, Emre NC, Ceribelli M, Zhang M, Wright G, Xiao W, Powell J, Platig J, Kohlhammer H, Young RM, Zhao H, Yang Y, Xu W, Buggy JJ, Balasubramanian S, Mathews LA, Shinn P, Guha R, Ferrer M, Thomas C, Waldmann TA, Staudt LM.
Cancer Cell. 2012 Jun 12;21(6):723-37. doi: 10.1016/j.ccr.2012.05.024.
PMID 22698399
 
A polymorphism in IRF4 affects human pigmentation through a tyrosinase-dependent MITF/TFAP2A pathway.
Praetorius C, Grill C, Stacey SN, Metcalf AM, Gorkin DU, Robinson KC, Van Otterloo E, Kim RS, Bergsteinsdottir K, Ogmundsdottir MH, Magnusdottir E, Mishra PJ, Davis SR, Guo T, Zaidi MR, Helgason AS, Sigurdsson MI, Meltzer PS, Merlino G, Petit V, Larue L, Loftus SK, Adams DR, Sobhiafshar U, Emre NC, Pavan WJ, Cornell R, Smith AG, McCallion AS, Fisher DE, Stefansson K, Sturm RA, Steingrimsson E.
Cell. 2013 Nov 21;155(5):1022-33. doi: 10.1016/j.cell.2013.10.022.
PMID 24267888
 
IRF4 transcription factor-dependent CD11b+ dendritic cells in human and mouse control mucosal IL-17 cytokine responses.
Schlitzer A, McGovern N, Teo P, Zelante T, Atarashi K, Low D, Ho AW, See P, Shin A, Wasan PS, Hoeffel G, Malleret B, Heiseke A, Chew S, Jardine L, Purvis HA, Hilkens CM, Tam J, Poidinger M, Stanley ER, Krug AB, Renia L, Sivasankar B, Ng LG, Collin M, Ricciardi-Castagnoli P, Honda K, Haniffa M, Ginhoux F.
Immunity. 2013 May 23;38(5):970-83. doi: 10.1016/j.immuni.2013.04.011.
PMID 23706669
 
A role for IRF4 in the development of CLL.
Shukla V, Ma S, Hardy RR, Joshi SS, Lu R.
Blood. 2013 Oct 17;122(16):2848-55. doi: 10.1182/blood-2013-03-492769. Epub 2013 Aug 7.
PMID 23926303
 
IRF4 controls the positioning of mature B cells in the lymphoid microenvironments by regulating NOTCH2 expression and activity.
Simonetti G, Carette A, Silva K, Wang H, De Silva NS, Heise N, Siebel CW, Shlomchik MJ, Klein U.
J Exp Med. 2013 Dec 16;210(13):2887-902. doi: 10.1084/jem.20131026. Epub 2013 Dec 9.
PMID 24323359
 
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Written01-2009Silvia Rasi, Gianluca Gaidano
Division of Hematology, Department of Clinical and Experimental Medicine & Center of Biotechnologies for Applied Medical Research, Amedeo Avogadro University of Eastern Piedmont, Via Solaroli 17, 28100 Novara, Italy
Updated02-2014Vipul Shukla, Runqing Lu
Department of Genetics, Cell Biology & Anatomy, University of Nebraska Medical Center, Omaha, NE 68118, USA

Citation

This paper should be referenced as such :
Rasi, S ; Gaidano, G
IRF4 (interferon regulatory factor 4)
Atlas Genet Cytogenet Oncol Haematol. 2009;13(12):941-943.
Free online version   Free pdf version   [Bibliographic record ]
Atlas Genet Cytogenet Oncol Haematol. January 2009
URL : http://AtlasGeneticsOncology.org/Genes/IRF4ID231ch6p25.html

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