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BMC Cancer
Published in: BMC Cancer 1/2013

Open Access 01-12-2013 | Research article

Overexpression of primary microRNA 221/222 in acute myeloid leukemia

Authors: Anna Rommer, Katarina Steinleitner, Hubert Hackl, Christine Schneckenleithner, Maria Engelmann, Marcel Scheideler, Irena Vlatkovic, Robert Kralovics, Sabine Cerny-Reiterer, Peter Valent, Heinz Sill, Rotraud Wieser

Published in: BMC Cancer | Issue 1/2013

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Abstract

Background

Acute myeloid leukemia (AML) is a hematopoietic malignancy with a dismal outcome in the majority of cases. A detailed understanding of the genetic alterations and gene expression changes that contribute to its pathogenesis is important to improve prognostication, disease monitoring, and therapy. In this context, leukemia-associated misexpression of microRNAs (miRNAs) has been studied, but no coherent picture has emerged yet, thus warranting further investigations.

Methods

The expression of 636 human miRNAs was compared between samples from 52 patients with AML and 13 healthy individuals by highly specific locked nucleic acid (LNA) based microarray technology. The levels of individual mature miRNAs and of primary miRNAs (pri-miRs) were determined by quantitative reverse transcriptase (qRT) PCR. Transfections and infections of human cell lines were performed using standard procedures.

Results

64 miRNAs were significantly differentially expressed between AML and controls. Further studies on the clustered miRNAs 221 and 222, already known to act as oncogenes in other tumor types, revealed a deficiency of human myeloid cell lines to process vector derived precursor transcripts. Moreover, endogenous pri-miR-221/222 was overexpressed to a substantially higher extent than its mature products in most primary AML samples, indicating that its transcription was enhanced, but processing was rate limiting, in these cells. Comparison of samples from the times of diagnosis, remission, and relapse of AML demonstrated that pri-miR-221/222 levels faithfully reflected the stage of disease.

Conclusions

Expression of some miRNAs is strongly regulated at the posttranscriptional level in AML. Pri-miR-221/222 represents a novel molecular marker and putative oncogene in this disease.
Appendix
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Metadata
Title
Overexpression of primary microRNA 221/222 in acute myeloid leukemia
Authors
Anna Rommer
Katarina Steinleitner
Hubert Hackl
Christine Schneckenleithner
Maria Engelmann
Marcel Scheideler
Irena Vlatkovic
Robert Kralovics
Sabine Cerny-Reiterer
Peter Valent
Heinz Sill
Rotraud Wieser
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-13-364

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