# IRF4

Source: https://onco.cc/targets/irf4/  
OnCo record `irf4` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

IRF4 is a master transcription factor of plasma cells and a protein myeloma cells cannot do without. Lenalidomide and its successors lower IRF4 by destroying the two factors, Ikaros and Aiolos, that keep it switched on.

## Summary

IRF4 (chromosome 6p25.3) is a transcriptional activator that binds the interferon-stimulated response element of the MHC class I promoter and, with PU.1, the immunoglobulin lambda light-chain enhancer; it acts in lymphoid-specific signalling and, in complex with the BATF-JUNB heterodimer at AICE elements, in CD8 dendritic-cell differentiation (UniProt Q15306). In OnCo it is the downstream node of the immunomodulatory drugs: lenalidomide and golcadomide degrade Ikaros and Aiolos through cereblon, IRF4 and MYC fall, and the myeloma cell dies (lenalidomide mechanism steps).

## Fields

- Kind: Target
- Last checked: 2026-09-22
- Also known as: MUM1; LSIRF; interferon regulatory factor 4
- Tags: wave5-target
- Symbol: IRF4
- Class: transcription
- Biology: IRF4 is not bound by any corpus drug; it is lowered as a consequence of Ikaros and Aiolos degradation, which is why it sits at the end of the immunomodulatory drug mechanism alongside MYC.
- Where found: Multiple myeloma (dependency; lowered by immunomodulatory drugs); Diffuse large B-cell lymphoma (golcadomide trials)

## Notes

- Prevalence not recorded in this wave: HGNC and UniProt carry no positivity rates and no other source was consulted.
- Lymphoma, HTLV-1, Tax and HBZ: Human T-lymphotropic virus 1 integrates into the genome of a CD4 T cell and expresses Tax, which switches on NF-kB and interferes with the DNA-damage response and the spindle checkpoint, and HBZ, encoded on the opposite strand, which is retained when Tax expression is switched off under immune pressure. The host genome then acquires the rest of the lesions, and they are not random: the alterations found across 426 cases overlap significantly with the proteins Tax itself binds, and are concentrated in T-cell receptor and NF-kB signalling, T-cell trafficking and immune surveillance, with activating mutations in PLCG1, PRKCB, CARD11, VAV1, IRF4, FYN, CCR4 and CCR7, CTLA4-CD28 and ICOS-CD28 fusions, and intragenic deletions of IKZF2, CARD11 and TP73 (Kataoka 2015). Frequency: Across 426 adult T-cell leukaemia/lymphoma cases analysed by whole-genome, exome, transcriptome and targeted sequencing with copy-number and methylation arrays (Kataoka 2015). Most people infected with HTLV-1 never develop the disease, and the latency between infection, usually in infancy through breastfeeding, and the leukaemia is measured in decades. What it changes about treatment: The CCR4 finding is the practical one: CCR4 is both frequently expressed and frequently mutated, and mogamulizumab is used in this disease. The virus itself is not a drug target, and antiretroviral treatment does not cure the leukaemia.

## Sources

- HGNC HGNC:6119: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:6119
- UniProt Q15306: https://www.uniprot.org/uniprotkb/Q15306/entry
- NCBI Gene 3662: https://www.ncbi.nlm.nih.gov/gene/3662
- Kataoka et al., Nat Genet 2015: integrated molecular analysis of 426 adult T-cell leukaemia/lymphoma cases: https://doi.org/10.1038/ng.3415

## Connected records

- drugs: [Golcadomide](https://onco.cc/drugs/golcadomide/), [Lenalidomide](https://onco.cc/drugs/lenalidomide/)
- targets: [IKZF1 (Ikaros)](https://onco.cc/targets/ikzf1/), [IKZF3 (Aiolos)](https://onco.cc/targets/ikzf3/)
- pathways: [Inflammation & NF-κB](https://onco.cc/pathways/inflammation-nfkb/), [MYC](https://onco.cc/pathways/myc/), [Oncogenic viruses](https://onco.cc/pathways/oncogenic-viruses/), [Transcriptional machinery & addiction](https://onco.cc/pathways/transcription-addiction/)
- cancers: [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [Multiple myeloma](https://onco.cc/cancers/multiple-myeloma/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)](https://onco.cc/cancers/peripheral-t-cell-lymphoma/)
- technologies: [Cereblon E3 ligase modulators (CELMoDs)](https://onco.cc/technologies/celmods/)
- terms: [HTLV-1, Tax and HBZ in adult T-cell leukaemia/lymphoma](https://onco.cc/terms/lymphoma-bio-htlv1/)

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