Overexpression of primary microRNA 221/222 in acute myeloid leukemia
1 Department of Medicine I, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
2 Comprehensive Cancer Center of the Medical University of Vienna, Vienna, Austria
3 Biocenter, Division of Bioinformatics, Innsbruck Medical University, Innrain 80, 6020 Innsbruck, Austria
4 Present address: Institute of Pharmacology and Toxicology, University of Veterinary Medicine, Vienna, Austria
5 Institute for Genomics and Bioinformatics, Graz University of Technology, Petersgasse 14, 8010 Graz, Austria
6 Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, Vienna, Austria
7 Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
8 Ludwig Boltzmann Cluster Oncology, Währinger Gürtel 18-20, 1090 Vienna, Austria
9 Division of Hematology, Medical University of Graz, Auenbruggerplatz 38, 8036 Graz, Austria
BMC Cancer 2013, 13:364 doi:10.1186/1471-2407-13-364Published: 29 July 2013
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.
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.
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.
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.