ArticleLeukemia2010
Wilms' tumor gene 1 protein represses the expression of the tumor suppressor interferon regulatory factor 8 in human hematopoietic progenitors and in leukemic cells.
Article in Leukemia, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 27 citations in OpenAlex.
- First-in-human study of WT1 recombinant protein vaccination in elderly patients with AML in remission: a single-center experience.Cancer immunology, immunotherapy : CII · 2022Trial
- Article
- Identification ofBiomarker research · 2019Article
- Polymorphisms in the Wilms Tumor Gene Are Associated With Interindividual Variations in Rubella Virus-Specific Cellular Immunity After Measles-Mumps-Rubella II Vaccination.The Journal of infectious diseases · 2018Article
- The transcriptional coregulatorOncotarget · 2017Article
- Distinct global binding patterns of the Wilms tumor gene 1 (WT1) -KTS and +KTS isoforms in leukemic cells.Haematologica · 2017Article
- Relevance of Interferon Regulatory Factor-8 Expression in Myeloid-Tumor Interactions.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2016Review
- Deficiency in WT1-targeting microRNA-125a leads to myeloid malignancies and urogenital abnormalities.Oncogene · 2016Article
- WT1 Expression in Adult Acute Myeloid Leukemia: Assessing its Presence, Magnitude and Temporal Changes as Prognostic Factors.Pathology oncology research : POR · 2016Article
- WT1-mediated repression of the proapoptotic transcription factor ZNF224 is triggered by the BCR-ABL oncogene.Oncotarget · 2015Article
- Regulation of myelopoiesis by the transcription factor IRF8.International journal of hematology · 2015Review
- Article
- Regulation of the interferon regulatory factor-8 (IRF-8) tumor suppressor gene by the signal transducer and activator of transcription 5 (STAT5) transcription factor in chronic myeloid leukemia.The Journal of biological chemistry · 2014Article
- Interferon regulatory factor-8 is important for histone deacetylase inhibitor-mediated antitumor activity.PloS one · 2012Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Wilms' tumor gene 1 (WT1) is a transcription factor involved in developmental processes. In adult hematopoiesis, only a small portion of early progenitor cells express WT1, whereas most leukemias show persistently high levels, suggesting an oncogenic role. We have previously characterized oncogenic BCR/ABL1 tyrosine kinase signaling pathways for increased WT1 expression. In this study, we show that overexpression of BCR/ABL1 in CD34+ progenitor cells leads to reduced expression of interferon regulatory factor 8 (IRF8), in addition to increased WT1 expression. Interestingly, IRF8 is known as a tumor suppressor in some leukemias and we investigated whether WT1 might repress IRF8 expression. When analyzed in four leukemia mRNA expression data sets, WT1 and IRF8 were anticorrelated. Upon overexpression in CD34+ progenitors, as well as in U937 cells, WT1 strongly downregulated IRF8 expression. All four major WT1 splice variants induced repression, but not the zinc-finger-deleted WT1 mutant, indicating dependence on DNA binding. A reporter construct with the IRF8 promoter was repressed by WT1, dependent on a putative WT1-response element. Binding of WT1 to the IRF8 promoter was demonstrated by chromatin immunoprecipitation. Our results identify IRF8 as a direct target gene for WT1 and provide a possible mechanism for oncogenic effects of WT1 in leukemia.
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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.