https://scholars.lib.ntu.edu.tw/handle/123456789/629030
標題: | The N-terminal CEBPA mutant in acute myeloid leukemia impairs CXCR4 expression | 作者: | YUAN-YEH KUO HSIN-AN HOU YIN-KAI CHEN Li, Li-Yu Chen, Po-Hsuen Tseng, Mei-Hsuan Huang, Chi-Fei Lee, Fen-Yu Liu, Ming-Chih Liu, Chia-Wen WEN-CHIEN CHOU Liu, Chieh-Yu JIH-LUH TANG MING YAO HWEI-FANG TIEN |
關鍵字: | ACUTE MYELOGENOUS LEUKEMIA; PRIMARY MYELODYSPLASTIC SYNDROME; DISEASE PROGRESSION; FAVORABLE PROGNOSIS; DOUBLE MUTATIONS; NORMAL KARYOTYPE; C/EBP-ALPHA; CELLS; AML; STABILITY | 公開日期: | 十二月-2014 | 出版社: | FERRATA STORTI FOUNDATION | 卷: | 99 | 期: | 12 | 起(迄)頁: | 1799 | 來源出版物: | Haematologica | 摘要: | CXC chemokine receptor 4 (CXCR4) is an essential regulator for homing and maintenance of hematopoietic stem cells within the bone marrow niches. Analysis of clinical implications of bone marrow CXCR4 expression in patients with acute myeloid leukemia showed not only higher CXCR4 expression was an independent poor prognostic factor, irrespective of age, white blood cell counts, cytogenetics, and mutation status of NPM1/FLT3-ITD and CEBPA, but also showed CXCR4 expression was inversely associated with mutations of CEBPA, a gene encoding transcription factor C/EBPα. Patients with wild-type CEBPA had significantly higher CXCR4 expression than those with mutated CEBPA. We hypothesized that CEBPA might influence the expression of CXCR4. To test this hypothesis, we first examined endogenous CXCR4 expression in 293T and K562 cells over-expressing wild-type C/EBPα p42 and demonstrated that CXCR4 levels were increased in these cells, whilst the expression of the N-terminal mutant, C/EBPα p30, diminished CXCR4 transcription. We further showed p42 was bound to the CXCR4 promoter by the chromatin immunoprecipitation assays. Induction of p42 in the inducible K562-C/EBPα cell lines increased the chemotactic migration. Moreover, decreased expression of C/EBPα by RNA interference decreased levels of CXCR4 protein expression in U937 cells, thereby abrogating CXCR4-mediated chemotaxis. Our results provide, for the first time, evidence that C/EBPα indeed regulates the activation of CXCR4, which is critical for the homing and engraftment of acute myeloid leukemia cells, while p30 mutant impairs CXCR4 expression. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/629030 | ISSN: | 0390-6078 | DOI: | 10.3324/haematol.2014.107821 |
顯示於: | 醫學系 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。