title: [Effect of AML1-ETO fusion protein on the expression of BCL-2].
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.
authors.affiliation: Medical Ecsomatics College of Beihua University, Jilin 132013, Jilin Province, China.
authors.forename: Wen-Yue
authors.initials: WY
authors.lastname: Zhuang
authors.affiliation: Department of Laboratorial Examination, Jilin Medical College, Jilin 132013, Jilin Province, China.
authors.forename: Zheng-Yi
authors.initials: ZY
authors.lastname: Li
authors.affiliation: Cyrus Tang Hematology Center of Soochow University, Suzhou 215000, Jiangsu Province, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou 215000, Jiangsu Province, China.
authors.forename: Jian-Nong
authors.initials: JN
authors.lastname: Cen
authors.affiliation: Department of Cell Biology, School of Biology & Basic Medical Science, Soochow University, Suzhou 215000, Jiangsu Province, China.
authors.forename: Wen-Zhuo
authors.initials: WZ
authors.lastname: Zhuang
authors.affiliation: Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou 215000, Jiangsu Province, China. E-mail: szchenzx@ 263.net.
authors.forename: Zi-Xing
authors.initials: ZX
authors.lastname: Chen
mesh_terms: D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism*; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism*; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D000075142:RUNX1 Translocation Partner 1 Protein; D020298:U937 Cells
chemical_list: C107844:AML1-ETO fusion protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; D019253:Proto-Oncogene Proteins c-bcl-2; D000075142:RUNX1 Translocation Partner 1 Protein