Aberrant expression of mir-9/9* in myeloid progenitors inhibits neutrophil differentiation by post-transcriptional regulation of erg

ABSTRACT Aberrant post-transcriptional regulation by microRNAs (miRNAs) has been shown to be involved in the pathogenesis of acute myeloid leukemia (AML). In a previous study, we performed a

large functional screen using a retroviral barcoded miRNA expression library. Here, we report that overexpression of miR-9/9* in myeloid 32D cell line (32D-miR-9/9*) had profound impact on

granulocyte colony-stimulating factor-induced differentiation. Further _in vitro_ studies showed that enforced expression of miR-9/9* blocked normal neutrophil development in 32D and in

primary murine lineage-negative bone marrow cells. We examined the expression of miR-9/9* in a cohort of 647 primary human AMLs. In most cases, miR-9 and miR-9* were significantly

upregulated and their expression levels varied according to AML subtype, with the highest expression in _MLL_-related leukemias harboring 11q23 abnormalities and the lowest expression in AML

cases with t(8;21) and biallelic mutations in _CEBPA_. Gene expression profiling of AMLs with high expression of miR-9/9* and 32D-miR-9/9* identified ETS-related gene (_Erg_) as the only

common potential target. Upregulation of ERG in 32D cells rescued miR-9/9*-induced block in neutrophil differentiation. Taken together, this study demonstrates that miR-9/9* are aberrantly

expressed in most of AML cases and interfere with normal neutrophil differentiation by downregulation of ERG. Access through your institution Buy or subscribe This is a preview of

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ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS OVEREXPRESSION OF MIR-99A

PROMOTED EXPANSION AND SUPPRESSED DIFFERENTIATION OF HEMATOPOIETIC STEM/PROGENITOR CELLS Article Open access 14 March 2025 THE PROTO-ONCOGENIC MIR-106A-363 CLUSTER ENHANCES ADVERSE RISK

ACUTE MYELOID LEUKEMIA THROUGH MITOCHONDRIAL ACTIVATION Article 17 March 2025 EXPLORING THE POTENTIAL OF PREDICTED MIRNAS ON THE GENES INVOLVED IN THE EXPANSION OF HEMATOPOIETIC STEM CELLS

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molecular signatures of high ERG leukemias. _Leukemia_ 2014; 29: 819–827. Article  Google Scholar  Download references ACKNOWLEDGEMENTS This study was supported in part by an Erasmus MC

grant (to MJL), Dutch Cancer Society grant (EMCR2009-4472 to MJL) and the Deutsche Forschungsgemeinschaft (SFB 1074 project B03 to LB). LB was supported in part by the Deutsche

Forschungsgemeinschaft (Heisenberg-Stipendium BU 1339/3-1). We thank Dr VHJ van der Velden for help with flow cytometric analysis, Dr PJM Valk for providing the Dutch AML data set and

critical revision of the manuscript and Professor Dr HR Delwel for his mentorship and contribution to interpretation of the data. AUTHOR CONTRIBUTIONS KN and SMS planned, carried out the

experiments and analyzed the data. LB and HD provided the German data set and carried out experiments. KvL performed morphological evaluation and quantification of cytospins. SJE, CE and MKD

performed experiments. EMJB, SJE, HD, LB, BL and MJL designed the study and interpreted the results. KN, SMS, SJE, LB, HD, BL and MJL wrote or contributed to the manuscript. AUTHOR

INFORMATION Author notes * K Nowek and S M Sun: These authors contributed equally to this work. AUTHORS AND AFFILIATIONS * Department of Hematology, Erasmus University Medical Center Cancer

Institute, Rotterdam, The Netherlands K Nowek, S M Sun, E M J Bindels, C Exalto, M K Dijkstra, K van Lom, S J Erkeland, B Löwenberg & M Jongen-Lavrencic * Department of Internal Medicine

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AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Nowek, K., Sun, S., Bullinger, L. _et al._ Aberrant expression of miR-9/9* in myeloid progenitors inhibits

neutrophil differentiation by post-transcriptional regulation of ERG. _Leukemia_ 30, 229–237 (2016). https://doi.org/10.1038/leu.2015.183 Download citation * Received: 20 January 2015 *

Revised: 18 June 2015 * Accepted: 22 June 2015 * Published: 15 July 2015 * Issue Date: January 2016 * DOI: https://doi.org/10.1038/leu.2015.183 SHARE THIS ARTICLE Anyone you share the

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