ArticleLeukemia2017
Citrullination of histone H3 drives IL-6 production by bone marrow mesenchymal stem cells in MGUS and multiple myeloma.
Article in Leukemia, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Role of the PADI family in inflammatory autoimmune diseases and cancers: A systematic review.Frontiers in immunology · 2023Pooled it
- Targeting Peptidylarginine Deiminases in Neurons and Astrocytes in Central Nervous System Injury-Effects of Pan-PAD Inhibitor Cl-Amidine in an Oxygen-Glucose Deprivation Model of Ischaemia (OGD/R) and LPS Stimulation In Vitro.International journal of molecular sciences · 2026Article
- Regulation of basal and tumour necrosis factor α-induced fibroblast gene expression by peptidylarginine deiminase 2.The Journal of physiology · 2026Article
- Mesenchymal Stromal Cells: Bridging the Gaps in Hematologic Disease Therapy.Stem cell reviews and reports · 2026Review
- Humanized Bone Model Identifies BMP6 as a Multifunctional Regulator in Myeloma Bone Disease.Biomolecules · 2025Article
- Article
- Citrullination in health and disease: From physiological function to gene regulation.Genes & diseases · 2025Review
- Multiple myeloma with 1q gain/amplification exhibits reduced CD38 expression via interleukin-6 receptor overexpression.British journal of haematology · 2025Article
- Crossing epigenetic frontiers: the intersection of novel histone modifications and diseases.Signal transduction and targeted therapy · 2024Review
- Differential Responses to Aging Among the Transcriptome and Proteome of Mesenchymal Progenitor Populations.The journals of gerontology. Series A, Biological sciences and medical sciences · 2024Article
- Inhibition of glutaminolysis alone and in combination with HDAC inhibitor has anti-myeloma therapeutic effects.Cancer drug resistance (Alhambra, Calif.) · 2024Article
- Differential responses to aging amongst the transcriptome and proteome of mesenchymal progenitor populations.Research square · 2023Article
- Review
- Small molecule activates citrullination through targeting PAD2.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Article
- Inflammatory Bone Marrow Mesenchymal Stem Cells in Multiple Myeloma: Transcriptional Signature and In Vitro Modeling.Cancers · 2023Article
- Mathematical reconstruction of the metabolic network in an in-vitro multiple myeloma model.PLoS computational biology · 2023Article
- The virtues and vices of protein citrullination.Royal Society open science · 2022Review
- H3K4 methylation by SETD1A/BOD1L facilitates RIF1-dependent NHEJ.Molecular cell · 2022Article
- Identification of super-enhancer-driven peptidyl arginine deiminases as potential biomarkers and therapeutic targets for osimertinib-resistant non-small cell lung cancer.Frontiers in pharmacology · 2022Article
- Histone citrullination: a new target for tumors.Molecular cancer · 2021Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Multiple myeloma (MM), an incurable plasma cell malignancy, requires localisation within the bone marrow. This microenvironment facilitates crucial interactions between the cancer cells and stromal cell types that permit the tumour to survive and proliferate. There is increasing evidence that the bone marrow mesenchymal stem cell (BMMSC) is stably altered in patients with MM-a phenotype also postulated to exist in patients with monoclonal gammopathy of undetermined significance (MGUS) a benign condition that precedes MM. In this study, we describe a mechanism by which increased expression of peptidyl arginine deiminase 2 (PADI2) by BMMSCs in patients with MGUS and MM directly alters malignant plasma cell phenotype. We identify PADI2 as one of the most highly upregulated transcripts in BMMSCs from both MGUS and MM patients, and that through its enzymatic deimination of histone H3 arginine 26, PADI2 activity directly induces the upregulation of interleukin-6 expression. This leads to the acquisition of resistance to the chemotherapeutic agent, bortezomib, by malignant plasma cells. We therefore describe a novel mechanism by which BMMSC dysfunction in patients with MGUS and MM directly leads to pro-malignancy signalling through the citrullination of histone H3R26.
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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.