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|Title:||C/EBPα regulated microRNA-34a targets E2F3 during granulopoiesis and is down-regulated in AML with CEBPA mutations||Authors:||Pulikkan, J.A.
|Issue Date:||16-Dec-2010||Citation:||Pulikkan, J.A., Peramangalam, P.S., Dengler, V., Ho, P.A., Preudhomme, C., Meshinchi, S., Christopeit, M., Nibourel, O., Müller-Tidow, C., Bohlander, S.K., Tenen, D.G., Behre, G. (2010-12-16). C/EBPα regulated microRNA-34a targets E2F3 during granulopoiesis and is down-regulated in AML with CEBPA mutations. Blood 116 (25) : 5638-5649. ScholarBank@NUS Repository. https://doi.org/10.1182/blood-2010-04-281600||Abstract:||The transcription factor, CCAAT enhancer binding protein alpha (C/EBPα), is crucial for granulopoiesis and is deregulated by various mechanisms in acute myeloid leukemia (AML). Mutations in the CEBPA gene are reported in 10% of human patients with AML. Even though the C/EBPα mutants are known to display distinct biologic function during leukemogenesis, the molecular basis for this subtype of AML remains elusive.We have recently showed the significance of deregulation of C/EBPα-regulated microRNA (miR) in AML. In this study, we report that miR-34a is a novel target of C/EBPα in granulopoiesis. During granulopoiesis, miR-34a targets E2F3 and blocks myeloid cell proliferation. Analysis of AML samples with CEBPA mutations revealed a lower expression of miR-34a and elevated levels of E2F3 as well as E2F1, a transcriptional target of E2F3. Manipulation of miR-34a reprograms granulocytic differentiation of AML blast cells with CEBPA mutations. These results define miR-34a as a novel therapeutic target in AML with CEBPA mutations. © 2010 by The American Society of Hematology.||Source Title:||Blood||URI:||http://scholarbank.nus.edu.sg/handle/10635/125363||ISSN:||00064971||DOI:||10.1182/blood-2010-04-281600|
|Appears in Collections:||Staff Publications|
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