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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
C/EBPα-regulated microRNA-34a targets E2F3 during granulopoiesis and is downregulated in AML with CEBPA mutations.
Blood 116, 5638-5649 (2010)
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DOI
PMC
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 biological 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 re-programmes granulocytic differentiation of AML blast cells with CEBPA mutations. These results define miR-34a as a novel therapeutic target in AML with CEBPA mutations.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
ISSN (print) / ISBN
0006-4971
e-ISSN
1528-0020
Zeitschrift
Blood
Quellenangaben
Band: 116,
Heft: 25,
Seiten: 5638-5649
Verlag
American Society of Hematology
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed