Activation of NF-κB driven inflammatory programs in mesenchymal elements attenuates hematopoiesis in low-risk myelodysplastic syndromes

• Published in: Leukemia Vol. 33; no. 2; pp. 536 - 541
• Main Authors: Ping, Zhen, Chen, Si, Hermans, Sjoerd J. F., Kenswil, Keane J. G., Feyen, Jacqueline, van Dijk, Claire, Bindels, Eric M. J., Mylona, Athina M., Adisty, Niken M., Hoogenboezem, Remco M., Sanders, Mathijs A., Cremers, Eline M. P., Lindenbergh-Kortleve, Dicky J., Samsom, Janneke N., van de Loosdrecht, Arjan A., Raaijmakers, Marc H. G. P.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-02-2019; Nature Publishing Group
• Subjects: 13/100; 13/106; 13/31; 13/51; 14/19; 38/91; 631/532/1542; 631/67/327; 692/699/1541/1990/1673; 82/80; Activation; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Brief Communication; Cancer Research; Case-Control Studies; Cells, Cultured; Critical Care Medicine; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Hematology; Hematopoiesis; Humans; Inflammation; Inflammation Mediators - metabolism; Intensive; Internal Medicine; Medicine; Medicine & Public Health; Mesenchymal Stem Cells - immunology; Mesenchymal Stem Cells - metabolism; Mesenchymal Stem Cells - pathology; Mesenchyme; Myelodysplastic syndrome; Myelodysplastic syndromes; Myelodysplastic Syndromes - genetics; Myelodysplastic Syndromes - immunology; Myelodysplastic Syndromes - metabolism; Myelodysplastic Syndromes - pathology; NF-kappa B - genetics; NF-kappa B - metabolism; NF-κB protein; Oncology; Oxidation; Prognosis; Regulators; Risk Factors; Transcription
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/s41375-018-0267-x

Highlights
Activation of NF-κB signaling in mesenchymal cells is common in LR-MDS.
Activation of NF-κB in mesenchymal cells leads to transcriptional overexpression of inflammatory factors including negative regulators of hematopoiesis.
Activation of NF-κB attenuates HSPC numbers and function ex vivo.