ArticleCancer research2011
IRF8 regulates acid ceramidase expression to mediate apoptosis and suppresses myelogeneous leukemia.
Article in Cancer research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 73 citations in OpenAlex.
- TCEA1 Suppresses Acute Promyelocytic Leukemia by Upregulating C/EBPε and IRF8.International journal of molecular sciences · 2026Article
- Rhinovirus infection promotes suppression of sphingosine and enhanced bacterial infection in cystic fibrosis airways.The Journal of biological chemistry · 2026Article
- Microbial riboflavin inhibits ceramide synthase 3 to lower ceramide (d18:1/26:0) and delay colorectal cancer progression.Cell metabolism · 2025Article
- The multiple roles of interferon regulatory factor family in health and disease.Signal transduction and targeted therapy · 2024Review
- IgA nephropathy.Nature reviews. Disease primers · 2023Review
- Natural Products and Small Molecules Targeting Cellular Ceramide Metabolism to Enhance Apoptosis in Cancer Cells.Cancers · 2023Review
- Silencing of IRF8 Mediated by m6A Modification Promotes the Progression of T-Cell Acute Lymphoblastic Leukemia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Advancements on the Multifaceted Roles of Sphingolipids in Hematological Malignancies.International journal of molecular sciences · 2022Review
- Harnessing the power of sphingolipids: Prospects for acute myeloid leukemia.Blood reviews · 2022Review
- Review
- Epigenetic modifications in the accumulation and function of myeloid-derived suppressor cells.Frontiers in immunology · 2022Review
- High IRF8 expression correlates with CD8 T cell infiltration and is a predictive biomarker of therapy response in ER-negative breast cancer.Breast cancer research : BCR · 2021Article
- Autocrine IL6-Mediated Activation of the STAT3-DNMT Axis Silences the TNFα-RIP1 Necroptosis Pathway to Sustain Survival and Accumulation of Myeloid-Derived Suppressor Cells.Cancer research · 2020Article
- Human Endometrial Transcriptome and Progesterone Receptor Cistrome Reveal Important Pathways and Epithelial Regulators.The Journal of clinical endocrinology and metabolism · 2020Article
- Acid ceramidase of macrophages traps herpes simplex virus in multivesicular bodies and protects from severe disease.Nature communications · 2020Article
- IRF8 induces senescence of lung cancer cells to exert its tumor suppressive function.Cell cycle (Georgetown, Tex.) · 2019Article
- TCEA1 regulates the proliferative potential of mouse myeloid cells.Experimental cell research · 2018Article
- Loss of acid ceramidase in myeloid cells suppresses intestinal neutrophil recruitment.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Pazopanib radio-sensitization of human sarcoma tumors.Oncotarget · 2018Article
- Interferon regulatory factor 8 regulates caspase-1 expression to facilitate Epstein-Barr virus reactivation in response to B cell receptor stimulation and chemical induction.PLoS pathogens · 2018Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
IFN regulatory factor 8 (IRF8) is a key transcription factor for myeloid cell differentiation and its expression is frequently lost in hematopoietic cells of human myeloid leukemia patients. IRF8-deficient mice exhibit uncontrolled clonal expansion of undifferentiated myeloid cells that can progress to a fatal blast crisis, thereby resembling human chronic myelogeneous leukemia (CML). Therefore, IRF8 is a myeloid leukemia suppressor. Whereas the understanding of IRF8 function in CML has recently improved, the molecular mechanisms underlying IRF8 function in CML are still largely unknown. In this study, we identified acid ceramidase (A-CDase) as a general transcription target of IRF8. We demonstrated that IRF8 expression is regulated by IRF8 promoter DNA methylation in myeloid leukemia cells. Restoration of IRF8 expression repressed A-CDase expression, resulting in C16 ceramide accumulation and increased sensitivity of CML cells to FasL-induced apoptosis. In myeloid cells derived from IRF8-deficient mice, A-CDase protein level was dramatically increased. Furthermore, we demonstrated that IRF8 directly binds to the A-CDase promoter. At the functional level, inhibition of A-CDase activity, silencing A-CDase expression, or application of exogenous C16 ceramide sensitized CML cells to FasL-induced apoptosis, whereas overexpression of A-CDase decreased CML cells' sensitivity to FasL-induced apoptosis. Consequently, restoration of IRF8 expression suppressed CML development in vivo at least partially through a Fas-dependent mechanism. In summary, our findings determine the mechanism of IRF8 downregulation in CML cells and they determine a primary pathway of resistance to Fas-mediated apoptosis and disease progression.
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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.