ArticleLeukemia2015
MMSET regulates expression of IRF4 in t(4;14) myeloma and its silencing potentiates the effect of bortezomib.
Article in Leukemia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
21 citing papers in PubMed, 34 citations in OpenAlex.
- NSD Family-Mediated H3K36 Methylation in Human Cancer: Mechanisms and Therapeutic Opportunities.Biomedicines · 2025Review
- LAMP5 modulates IRF4 stability and nuclear transport: a critical mechanism in myeloma progression and therapy.Oncogene · 2025Article
- Post-Translational Modifications in Multiple Myeloma: Mechanisms of Drug Resistance and Therapeutic Opportunities.Biomolecules · 2025Review
- Discovery of a novel class NSD2 inhibitor for multiple myeloma with t(4;14)Blood neoplasia · 2025Article
- Identification and validation of a histone modification-related gene signature to predict the prognosis of multiple myeloma.Frontiers in genetics · 2025Article
- Unlocking the therapeutic potential of selective CDK7 and BRD4 inhibition against multiple myeloma cell growth.Haematologica · 2025Article
- Class II ferroptosis inducers are a novel therapeutic approach for t(4;14)-positive multiple myeloma.Blood advances · 2024Article
- Review
- Review
- The fatty acid elongase ELOVL6 regulates bortezomib resistance in multiple myeloma.Blood advances · 2021Article
- Review
- Quantitative expression of Ikaros, IRF4, and PSMD10 proteins predicts survival in VRD-treated patients with multiple myeloma.Blood advances · 2020Article
- The Role of Methyltransferase NSD2 as a Potential Oncogene in Human Solid Tumors.OncoTargets and therapy · 2020Review
- Frequent upregulation of G9a promotes RelB-dependent proliferation and survival in multiple myeloma.Experimental hematology & oncology · 2020Article
- MMSET I acts as an oncoprotein and regulates GLO1 expression in t(4;14) multiple myeloma cells.Leukemia · 2019Article
- The biological significance of histone modifiers in multiple myeloma: clinical applications.Blood cancer journal · 2018Review
- Integrative network analysis identifies novel drivers of pathogenesis and progression in newly diagnosed multiple myeloma.Leukemia · 2018Article
- The Epigenome in Multiple Myeloma: Impact on Tumor Cell Plasticity and Drug Response.Frontiers in oncology · 2018Review
- Review
- MB4-2/MB4-3 transcripts ofOncotarget · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple myeloma (MM) is characterized by recurrent chromosomal translocations. In t(4;14) MM, the MM SET domain (MMSET) protein is universally overexpressed and has been suggested to have an important tumorigenic role. However, the exact molecular targets underlying MMSET activity are not well understood. Here, we found in t(4;14) MM cells that MMSET knockdown decreases interferon regulatory factor 4 (IRF4) expression, and ectopic MMSET increases IRF4 expression, suggesting that MMSET is an upstream regulator of IRF4. Further analyses indicated an interaction between MMSET and nuclear factor-κB, which both bind to the IRF4 promoter region. A luciferase reporter assay showed that MMSET is an important functional element for the IRF4 promoter. MMSET knockdown induces apoptosis and potentiates the effects of bortezomib in vitro and in vivo. Importantly, we found that bortezomib could reduce expression of MMSET and IRF4. This might partly explain the additive effect of combining MMSET knockdown and bortezomib treatment. These results identify MMSET as a key regulator involved in the regulatory network of transcription factor IRF4, which is critical for MM cell survival, suggesting that the combination of MMSET inhibition and bortezomib is likely to improve patient outcome in MM.
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Registered trials
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.