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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.
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.
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.
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
ISSN: 00064971
DOI: 10.1182/blood-2010-04-281600
Appears in Collections:Staff Publications

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