ArticleCell stem cell2021
Selective antisense oligonucleotide inhibition of human IRF4 prevents malignant myeloma regeneration via cell cycle disruption.
Article in Cell stem cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 60 citations in OpenAlex.
- Probiogenomic analysis of functional potential and safety ofMicrobiology spectrum · 2026Article
- Multiple myeloma: A tale of deregulated transcription factors.HemaSphere · 2026Review
- Pharmacological targeting of IRF4 as a therapeutic strategy for multiple myeloma.Nature chemical biology · 2026Article
- Optimal conditions for quantification of IRF4 mRNA and protein as a correlative biomarker in clinical cancer studies.Journal of translational medicine · 2026Article
- Pharmacological targeting of oncogenic condensates in cancer: mechanistic insights and therapeutic opportunities.Acta pharmacologica Sinica · 2026Review
- RNA-Based Therapeutic Strategies in Multiple Myeloma: From Molecular Targets to Delivery and Clinical Translation.International journal of molecular sciences · 2026Review
- IRF4 Promotes Immune Evasion and Shapes the Tumor Microenvironment in Follicular Lymphoma.Blood cancer discovery · 2025Article
- Whole-genome sequencing reveals three follicular lymphoma subtypes with distinct cell of origin and patient outcomes.Cell reports. Medicine · 2025Article
- Systemic deficits in lipid homeostasis promote aging-associated impairments in B cell progenitor development.GeroScience · 2025Article
- Loss of BCL7A permits IRF4 transcriptional activity and cellular growth in multiple myeloma.Blood · 2025Article
- Article
- Inhibition of interferon regulatory factor 4 orchestrates T cell dysfunction, extending mouse cardiac allograft survival.Chinese medical journal · 2025Article
- IRF4 contributes to chemoresistance in IGH::BCL2-positive diffuse large B-cell lymphomas by mediating BCL2-induced SOX9 expression.Clinical and translational medicine · 2025Article
- Discovery of a novel class NSD2 inhibitor for multiple myeloma with t(4;14)Blood neoplasia · 2025Article
- Interferon regulatory factor 4 mediates nonenzymatic IRE1 dependency in multiple myeloma cells.PLoS biology · 2025Article
- c-FOS Confers Stem Cell-like Features to Multiple Myeloma Cells in a Bone Marrow Microenvironment.Cells · 2025Article
- NSUN2 methylates IRF4 to affect the capacity of macrophages attached to titanium implant on osteogenic differentiation of PDLSCs and angiogenesis of HUVECs in vitro.BMC oral health · 2024Article
- Targeting splicing for hematological malignancies therapy.BMC genomics · 2024Review
- New opportunities to overcome T cell dysfunction: the role of transcription factors and how to target them.Trends in biochemical sciences · 2024Review
- The multiple roles of interferon regulatory factor family in health and disease.Signal transduction and targeted therapy · 2024Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
In multiple myeloma, inflammatory and anti-viral pathways promote disease progression and cancer stem cell generation. Using diverse pre-clinical models, we investigated the role of interferon regulatory factor 4 (IRF4) in myeloma progenitor regeneration. In a patient-derived xenograft model that recapitulates IRF4 pathway activation in human myeloma, we test the effects of IRF4 antisense oligonucleotides (ASOs) and identify a lead agent for clinical development (ION251). IRF4 overexpression expands myeloma progenitors, while IRF4 ASOs impair myeloma cell survival and reduce IRF4 and c-MYC expression. IRF4 ASO monotherapy impedes tumor formation and myeloma dissemination in xenograft models, improving animal survival. Moreover, IRF4 ASOs eradicate myeloma progenitors and malignant plasma cells while sparing normal human hematopoietic stem cell development. Mechanistically, IRF4 inhibition disrupts cell cycle progression, downregulates stem cell and cell adhesion transcript expression, and promotes sensitivity to myeloma drugs. These findings will enable rapid clinical development of selective IRF4 inhibitors to prevent myeloma progenitor-driven relapse.
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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.