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Acute Leukemias

The prognostic relevance of miR-212 expression with survival in cytogenetically and molecularly heterogeneous AML

Leukemia volume 27, pages 100–106 (2013)Cite this article

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Abstract

Acute myeloid leukemia (AML) is a highly heterogeneous disease, characterized by various cytogenetic and molecular abnormalities, many of which may express prognostic value. MicroRNAs (miRNAs) are a class of small regulatory RNAs. The prognostic value of miRNAs in AML is yet to be determined. Here, we set out to identify miRNAs that are consistent significant prognostic determinants, independent from other known prognostic factors. A discovery cohort (n=167) and validation cohort (n=409) of a heterogeneous AML population were used to reliably identify miRNAs with prognostic value. We report miR-212 as an independent prognostic factor, significantly associated with a prolonged overall survival (OS) and also event-free and relapse-free survival in a discovery cohort (hazard ratio (HR)s=0.77, P=0.015 for OS) that was subsequently confirmed in an independent validation cohort of 409 cases (HR=0.83, P=0.016). The prognostic significance and the prevalence of high miR-212 did not correlate with specific (cyto)genetic subtypes of AML. High miR-212 expression levels are associated with a gene expression profile that is significantly enriched for genes involved in the immune response. MiR-212 may improve the current prognostic risk stratification of mixed AML including normal karyotype AML and AML with cytogenetic and molecular abnormalities.

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Acknowledgements

We thank Wim van Putten from the HOVON data center for contribution to the statistical analysis and Peter Valk for molecular characterization of the HOVON AML samples and critical reviewing of the manuscript. This study was supported in part by the Erasmus MC grant (to MJL), the NutsOhra fund (project 1004–195 to MJL), the Deutsche José Carreras Stiftung e.V. (DJCLS R 06/41v to LB) and LB was supported in part by the Deutsche Forschungsgemeinschaft (Heisenberg-Stipendium BU 1339/3-1).

SMS planned and carried out the experiments and analyzed the data. VR took part in the analysis. LB and HD provided the German data set and carried out experiments. MKD performed experiments. HD, BL and MJL designed the study and interpreted the results. SMS, VR, LB, HD, BL and MJL wrote or contributed to the manuscript.

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Author notes

  1. S M Sun, V Rockova, B Löwenberg and M Jongen-Lavrencic: These authors contributed equally to this paper.

  2. These authors contributed equally to this paper.

Authors and Affiliations

  1. Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands

    S M Sun, V Rockova, M K Dijkstra, B Löwenberg & M Jongen-Lavrencic

  2. Department of Biostatistics, Erasmus University Medical Center, Rotterdam, The Netherlands

    V Rockova

  3. Department of Internal Medicine III, University of Ulm, Ulm, Germany

    L Bullinger & H Döhner

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  1. S M Sun
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Correspondence to M Jongen-Lavrencic.

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Sun, S., Rockova, V., Bullinger, L. et al. The prognostic relevance of miR-212 expression with survival in cytogenetically and molecularly heterogeneous AML. Leukemia 27, 100–106 (2013). https://doi.org/10.1038/leu.2012.158

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