Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive and largely incurable hematologic malignancy originating from plasmacytoid dendritic cells (pDCs). Using RNAi screening, we identified the E-box transcription factor TCF4 as a master regulator of the BPDCN oncogenic program. TCF4 served as a faithful diagnostic marker of BPDCN, and its downregulation caused the loss of the BPDCN-specific gene expression program and apoptosis. High-throughput drug screening revealed that bromodomain and extra-terminal domain inhibitors (BETis) induced BPDCN apoptosis, which was attributable to disruption of a BPDCN-specific transcriptional network controlled by TCF4-dependent super-enhancers. BETis retarded the growth of BPDCN xenografts, supporting their clinical evaluation in this recalcitrant malignancy.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5175469 | PMC |
| http://dx.doi.org/10.1016/j.ccell.2016.10.002 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
HBV and HBsAg strongly reshape the phenotype, function, and metabolism of DCs according to patients' clinical stage.
Hepatol Commun
February 2025
University Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Institute for Advanced Biosciences, Grenoble, France.
Background: Hepatitis B is a liver infection caused by HBV. Infected individuals who fail to control the viral infection develop chronic hepatitis B and are at risk of developing life-threatening liver diseases, such as cirrhosis or liver cancer. Dendritic cells (DCs) play important roles in the immune response against HBV but are functionally impaired in patients with chronic hepatitis B.
View Article and Find Full Text PDFBlastic plasmacytoid dendritic cell neoplasm: a Swiss case series of a very rare disease and a structured review of the literature.
Swiss Med Wkly
January 2025
Department of Internal Medicine, Clinic for Medical Oncology and Hematology, Municipal Hospital Zurich Triemli, Zurich, Switzerland.
Introduction: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a very rare disease, with unique diagnostic challenges and often dismal outcome. There are no widely accepted treatment guidelines available. Lymphoma-like regimens with or without autologous or allogenic transplantation were the cornerstone of most therapeutic concepts.
View Article and Find Full Text PDFDeep immunophenotyping of circulating immune cells in major depressive disorder patients reveals immune correlates of clinical course and treatment response.
Brain Behav Immun Health
February 2025
Department of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases-IRCAD, University of Eastern Piedmont, 28100, Novara, Italy.
Major Depressive Disorder (MDD) is a widespread psychiatric condition impacting social and occupational functioning, making it a leading cause of disability. The diagnosis of MDD remains clinical, based on the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria, as biomarkers have not yet been validated for diagnostic purposes or as predictors of treatment response. Traditional treatment strategies often follow a one-size-fits-all approach obtaining suboptimal outcomes for many patients who fail to experience response or recovery.
View Article and Find Full Text PDFThis 30-color panel was developed to enable the enumeration and purification of distinct circulating immune cell subsets implicated in the pathogenesis of systemic autoimmune diseases including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc; scleroderma), Sjögren's disease (SjD), idiopathic inflammatory myopathy (IIM), and others. While designed for application to peripheral blood mononuclear cells, the inclusion of CD45 coupled with the ability to extract cellular autofluorescence spectral signatures enables the application of this panel to other tissue types. Of the 30 total markers, this panel employs 18 markers to profile T cell subsets consisting of different memory subsets and T helper polarities, > 10 markers to profile B cell subsets including double-negative B cells, and a total of 8 lineage markers to identify immune lineages including monocyte and natural killer cell subsets, conventional dendritic cells, plasmacytoid dendritic cells, and basophils.
View Article and Find Full Text PDFRecent Advances in Our Understanding of Human Inflammatory Dendritic Cells in Human Immunodeficiency Virus Infection.
Viruses
January 2025
Centre for Virus Research, The Westmead Institute for Medical Research, Westmead 2145, Australia.
Anogenital inflammation is a critical risk factor for HIV acquisition. The primary preventative HIV intervention, pre-exposure prophylaxis (PrEP), is ineffective in blocking transmission in anogenital inflammation. Pre-existing sexually transmitted diseases (STIs) and anogenital microbiota dysbiosis are the leading causes of inflammation, where inflammation is extensive and often asymptomatic and undiagnosed.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!