ArticleThe Journal of biological chemistry2018
An activating mutation of interferon regulatory factor 4 (IRF4) in adult T-cell leukemia.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Spectrum of mutational signatures in T-cell lymphoma reveals a key role for UV radiation in cutaneous T-cell lymphoma.Scientific reports · 2021Pooled it
- Integrated Genomic and Tumor Microenvironment Subtyping Improved Risk Stratification in Primary Central Nervous System Lymphoma.American journal of hematology · 2026Article
- Review
- Novel mutations of SRPX facilitate the stemness and malignant progression of glioma.British journal of cancer · 2025Article
- Common skin cancers and their association with other non-cutaneous primary malignancies: a review of the literature.Medical oncology (Northwood, London, England) · 2024Review
- TCR Pathway Mutations in Mature T Cell Lymphomas.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- Alvocidib inhibits IRF4 expression via super-enhancer suppression and adult T-cell leukemia/lymphoma cell growth.Cancer science · 2022Article
- IRF4 as an Oncogenic Master Transcription Factor.Cancers · 2022Review
- The molecular basis for the development of adult T-cell leukemia/lymphoma in patients with an IRF4Protein science : a publication of the Protein Society · 2022Article
- Clinical application of genomic aberrations in adult T-cell leukemia/lymphoma.Journal of clinical and experimental hematopathology : JCEH · 2020Review
- Interferon regulatory factor 4 as a therapeutic target in adult T-cell leukemia lymphoma.Retrovirology · 2020Article
- Molecular biology of human T cell leukemia virus.Seminars in diagnostic pathology · 2020Review
- Updates in lymph node and skin pathology of adult T-cell leukemia/lymphoma, biomarkers, and beyond.Seminars in diagnostic pathology · 2020Review
- Cells of adult T-cell leukemia evade HTLV-1 Tax/NF-κB hyperactivation-induced senescence.Blood advances · 2019Article
- Article
- Review
- Therapeutic Targeting of IRFs: Pathway-Dependence or Structure-Based?Frontiers in immunology · 2018Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
The human T-cell leukemia virus-1 (HTLV-1) oncoprotein Tax drives cell proliferation and resistance to apoptosis early in the pathogenesis of adult T-cell leukemia (ATL). Subsequently, probably as a result of specific immunoediting, Tax expression is down-regulated and functionally replaced by somatic driver mutations of the host genome. Both amplification and point mutations of interferon regulatory factor 4 (IRF4) have been previously detected in ATL., K59R is the most common single-nucleotide variation of IRF4 and is found exclusively in ATL. High-throughput whole-exome sequencing revealed recurrent activating genetic alterations in the T-cell receptor, CD28, and NF-κB pathways. We found that IRF4, which is transcriptionally activated downstream of these pathways, is frequently mutated in ATL. IRF4 RNA, protein, and IRF4 transcriptional targets are uniformly elevated in HTLV-1-transformed cells and ATL cell lines, and IRF4 was bound to genomic regulatory DNA of many of these transcriptional targets in HTLV-1-transformed cell lines. We further noted that the K59R IRF4 mutant is expressed at higher levels in the nucleus than WT IRF4 and is transcriptionally more active. Expression of both WT and the K59R mutant of IRF4 from a constitutive promoter in retrovirally transduced murine bone marrow cells increased the abundance of T lymphocytes but not myeloid cells or B lymphocytes in mice. IRF4 may represent a therapeutic target in ATL because ATL cells select for a mutant of IRF4 with higher nuclear expression and transcriptional activity, and overexpression of IRF4 induces the expansion of T lymphocytes
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.