Effect of AML1-ETO fusion protein on the expression of BCL-2.
10.7534/j.issn.1009-2137.2013.06.006
- Author:
Wen-Yue ZHUANG
1
;
Zheng-Yi LI
2
;
Yun ZHAO
3
;
Jian-Nong CEN
4
;
Wen-Zhuo ZHUANG
5
;
Zi-Xing CHEN
6
Author Information
1. Medical Ecsomatics College of Beihua University, Jilin 132013, Jilin Province, China.
2. Department of Laboratorial Examination, Jilin Medical College, Jilin 132013, Jilin Province, China.
3. Cyrus Tang Hematology Center of Soochow University, Suzhou 215000, Jiangsu Province, China.
4. Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou 215000, Jiangsu Province, China.
5. Department of Cell Biology, School of Biology & Basic Medical Science, Soochow University, Suzhou 215000, Jiangsu Province, China.
6. Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou 215000, Jiangsu Province, China. E-mail: szchenzx@ 263.net.
- Publication Type:Journal Article
- MeSH:
Core Binding Factor Alpha 2 Subunit;
genetics;
metabolism;
Gene Expression Regulation, Leukemic;
Humans;
Leukemia, Myeloid, Acute;
genetics;
metabolism;
Oncogene Proteins, Fusion;
genetics;
metabolism;
Proto-Oncogene Proteins c-bcl-2;
metabolism;
RUNX1 Translocation Partner 1 Protein;
U937 Cells
- From:
Journal of Experimental Hematology
2013;21(6):1394-1398
- CountryChina
- Language:Chinese
-
Abstract:
This study was aimed to investigate the effect of AML1-ETO fusion protein on the anti-apoptotic gene BCL-2 in leukemic cells and to explore its role in leukemogenesis. The apoptotic levels of U937-WT, U937-Mock and U937-A/E1-4 cells were examined by flow cytometry. And cleaved caspase-3 protein expression was detected by Western blot. BCL-2 gene expression both in AML1-ETO-expressing cells or U937 nonexpressing cells and in leukemia cells of AML patients with or without t(8;21) was assessed by quantitative PCR. The chromatin immunoprecipitation (ChIP)-based PCR was used to investigate the direct interaction between the AML1-ETO and BCL-2 promoter in AML1-ETO positive leukemia cell line. The results indicated that in U937-A/E cells but not in U937-WT or U937-Mock cells, apoptotic cells statistically significantly increased, and AML1-ETO expression also significantly enhanced activation of caspase-3. AML1-ETO-expressing cell subclones displayed significantly low levels of BCL-2 mRNA in comparison with the non-transfected U937. In primary bone marrow cells of acute myeloid leukemia containing AML1-ETO, levels of BCL-2 mRNA were markedly lower as compared with other acute myeloid leukemias lacking this translocation. The enriched regions in transfected cells were located within BCL-2 promoter. It is concluded that BCL-2 is the direct target gene of AML1-ETO. AML1-ETO can down-regulate the expression of BCL-2.
