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| Title |
Hypermethylation of the GATA binding protein 4 (GATA4) promoter in Chinese pediatric acute myeloid leukemia
|
|---|---|
| Published in |
BMC Cancer, October 2015
|
| DOI | 10.1186/s12885-015-1760-5 |
| Pubmed ID | |
| Authors |
Yan-Fang Tao, Fang Fang, Shao-Yan Hu, Jun Lu, Lan Cao, Wen-Li Zhao, Pei-Fang Xiao, Zhi-Heng Li, Na-Na Wang, Li-Xiao Xu, Xiao-Juan Du, Li-Chao Sun, Yan-Hong Li, Yi-Ping Li, Yun-Yun Xu, Jian Ni, Jian Wang, Xing Feng, Jian Pan |
| Abstract |
Acute 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. Transcriptional 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. MSP 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). Epigenetic 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. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 50% |
| France | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 50% |
| Members of the public | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 36 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 36 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 6 | 17% |
| Student > Bachelor | 6 | 17% |
| Researcher | 6 | 17% |
| Student > Ph. D. Student | 4 | 11% |
| Student > Doctoral Student | 3 | 8% |
| Other | 5 | 14% |
| Unknown | 6 | 17% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 10 | 28% |
| Biochemistry, Genetics and Molecular Biology | 8 | 22% |
| Agricultural and Biological Sciences | 2 | 6% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 6% |
| Chemistry | 2 | 6% |
| Other | 4 | 11% |
| Unknown | 8 | 22% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 23 October 2015.
All research outputs
#17,775,656
of 22,830,751 outputs
Outputs from BMC Cancer
#4,966
of 8,306 outputs
Outputs of similar age
#190,782
of 283,225 outputs
Outputs of similar age from BMC Cancer
#122
of 230 outputs
Altmetric has tracked 22,830,751 research outputs across all sources so far. This one is in the 19th percentile – i.e., 19% of other outputs scored the same or lower than it.
So far Altmetric has tracked 8,306 research outputs from this source. They receive a mean Attention Score of 4.3. This one is in the 34th percentile – i.e., 34% of its peers scored the same or lower than it.
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