C/EBPα Regulated MicroRNA-34a Targets E2F3 During Granulopoiesis and is Down-regulated in AML with CEBPA Mutations

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2010 Oct 5

PMID 20889924

Citations 69

Authors

John A Pulikkan

Philomina S Peramangalam

Viola Dengler

Phoenix A Ho

Claude Preudhomme

Soheil Meshinchi

Maximilian Christopeit

Oliver Nibourel

Carsten Muller-Tidow

Stefan K Bohlander

Daniel G Tenen

Gerhard Behre

Affiliations

Soon will be listed here.

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.

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