ArticleBMC cancer2015
Hypermethylation of the GATA binding protein 4 (GATA4) promoter in Chinese pediatric acute myeloid leukemia.
Article in BMC cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 19 citations in OpenAlex.
- Identification of Novel DNA Methylation Prognostic Biomarkers for AML With Normal Cytogenetics.JCO clinical cancer informatics · 2024Article
- Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro.International journal of molecular sciences · 2023Article
- A comprehensive genome-wide analysis of long non-coding RNA and mRNA expression profiles of JAK2V617F-positive classical myeloproliferative neoplasms.Bioengineered · 2021Article
- A novel DNA methylation-based model that effectively predicts prognosis in hepatocellular carcinoma.Bioscience reports · 2021Article
- The transcriptional factor GATA-4 negatively regulates Hsp70 transcription in Crassostrea hongkongensis.Molecular biology reports · 2020Article
- Article
- Aberrant DNA Methylation in Acute Myeloid Leukemia and Its Clinical Implications.International journal of molecular sciences · 2019Review
- Osmotic modulation of chromatin impacts on efficiency and kinetics of cell fate modulation.Scientific reports · 2018Article
- Article
- Aberrant JAK/STAT Signaling Suppresses TFF1 and TFF2 through Epigenetic Silencing of GATA6 in Gastric Cancer.International journal of molecular sciences · 2016Article
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Authors and funding
19 authors at 4 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundAcute myeloid leukemia (AML) is the second-most common form of leukemia in children. Aberrant DNA methylation patterns are a characteristic feature of AML. GATA4 has been suggested to be a tumor suppressor gene regulated by promoter hypermethylation in various types of human cancers although the expression and promoter methylation of GATA4 in pediatric AML is still unclear.
methodsTranscriptional expression levels of GATA4 were evaluated by semi-quantitative and real-time PCR. Methylation status was investigated by methylation-specific PCR (MSP) and bisulfate genomic sequencing (BGS). The prognostic significance of GATA4 expression and promoter methylation was assessed in 105 cases of Chinese pediatric acute myeloid leukemia patients with clinical follow-up records.
resultsMSP and BGS analysis showed that the GATA4 gene promoter is hypermethylated in AML cells, such as the HL-60 and MV4-11 human myeloid leukemia cell lines. 5-Aza treatment significantly upregulated GATA4 expression in HL-60 and MV4-11 cells. Aberrant methylation of GATA4 was observed in 15.0 % (3/20) of the normal bone marrow control samples compared to 56.2 % (59/105) of the pediatric AML samples. GATA4 transcript levels were significantly decreased in AML patients (33.06 ± 70.94; P = 0.011) compared to normal bone marrow/idiopathic thrombocytopenic purpura controls (116.76 ± 105.39). GATA4 promoter methylation was correlated with patient leukocyte counts (WBC, white blood cells) (P = 0.035) and minimal residual disease MRD (P = 0.031). Kaplan-Meier survival analysis revealed significantly shorter overall survival time in patients with GATA4 promoter methylation (P = 0.014).
conclusionsEpigenetic inactivation of GATA4 by promoter hypermethylation was observed in both AML cell lines and pediatric AML samples; our study implicates GATA4 as a putative tumor suppressor gene in pediatric AML. In addition, our findings imply that GATA4 promoter methylation is correlated with WBC and MRD. Kaplan-Meier survival analysis revealed significantly shorter overall survival in pediatric AML with GATA4 promoter methylation but multivariate analysis shows that it is not an independent factor. However, further research focusing on the mechanism of GATA4 in pediatric leukemia is required.
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