ArticleProceedings of the National Academy of Sciences of the United States of America2004
The leukemic fusion gene AML1-MDS1-EVI1 suppresses CEBPA in acute myeloid leukemia by activation of Calreticulin.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 87 citations in OpenAlex.
- Trial
- C/EBPα deregulation as a paradigm for leukemogenesis.Leukemia · 2017Review
- Acute myeloid leukemia with t(3;21)(q26.2;q22) developing following low-dose methotrexate therapy for rheumatoid arthritis and expressing two AML1/MDS1/EVI1 fusion proteins: A case report.Oncology letters · 2017Article
- The significance of c.690G>T polymorphism (rs34529039) and expression of the CEBPA gene in ovarian cancer outcome.Oncotarget · 2016Article
- EVI1 Interferes with Myeloid Maturation via Transcriptional Repression of Cebpa, via Binding to Two Far Downstream Regulatory Elements.The Journal of biological chemistry · 2016Article
- Review
- Acetylation of C/EBPα inhibits its granulopoietic function.Nature communications · 2016Article
- Expressional profiles of transcription factors in the progression of Helicobacter pylori-associated gastric carcinoma based on protein/DNA array analysis.Medical oncology (Northwood, London, England) · 2015Article
- Evolved Cellular Mechanisms to Respond to Genotoxic Insults: Implications for Radiation-Induced Hematologic Malignancies.Radiation research · 2015Review
- Monocyte-macrophage differentiation of acute myeloid leukemia cell lines by small molecules identified through interrogation of the Connectivity Map database.Cell cycle (Georgetown, Tex.) · 2015Article
- The tumor suppressor gene DAPK2 is induced by the myeloid transcription factors PU.1 and C/EBPα during granulocytic differentiation but repressed by PML-RARα in APL.Journal of leukocyte biology · 2014Article
- Phosphorylation of serine 21 modulates the proliferation inhibitory more than the differentiation inducing effects of C/EBPα in K562 cells.Journal of cellular biochemistry · 2012Article
- Asthma and COPD - The C/EBP Connection.The open respiratory medicine journal · 2012Article
- Calreticulin is a negative regulator of bronchial smooth muscle cell proliferation.Journal of allergy · 2012Article
- Programmed cell removal: a new obstacle in the road to developing cancer.Nature reviews. Cancer · 2011Review
- CEBPA methylation as a prognostic biomarker in patients with de novo acute myeloid leukemia.Leukemia · 2011Article
- C/EBPα dysregulation in AML and ALL.Critical reviews in oncogenesis · 2011Review
- The biological effects of C/EBPalpha in K562 cells depend on the potency of the N-terminal regulatory region, not on specificity of the DNA binding domain.The Journal of biological chemistry · 2010Article
- The tumour-suppressive miR-29a/b1 cluster is regulated by CEBPA and blocked in human AML.British journal of cancer · 2010Article
- Chronic myeloid leukemia: mechanisms of blastic transformation.The Journal of clinical investigation · 2010Review
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The leukemic fusion gene AML1-MDS1-EVI1 (AME) encodes a chimeric transcription factor that results from the t(3,21)(q26;q22) translocation seen in patients with acute myeloid leukemia, with therapy-related myelodysplastic syndrome, or with chronic myeloid leukemia in blast crisis. The myeloid transcription factor CEBPA is crucial for normal granulopoiesis. Here, we found that conditional expression of AME suppresses CEBPA protein by 90.8% and DNA-binding activity by 93.9%. In contrast, CEBPA mRNA levels remained unchanged. In addition, we detected no differences in CEBPA mRNA levels in leukemic blasts of patients carrying the AME translocation (n = 8) compared to acute myeloid leukemia patients with a normal karyotype (n = 9). CEBPA protein and binding activity, however, were reduced significantly (100% and 92.1%, respectively) in AME patient samples. Furthermore, we observed that calreticulin (CRT), a putative inhibitor of CEBPA translation, was strongly activated after induction of AME in the cell-line system (14.8-fold) and in AME patient samples (12.2-fold). Moreover, inhibition of CRT by small interfering RNA powerfully restored CEBPA levels. These results identify CEBPA as a key target of the leukemic fusion protein AME and suggest that modulation of CEBPA by CRT may represent a mechanism involved in the differentiation block in AME leukemias.
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