title: Overexpression of primary microRNA 221/222 in acute myeloid leukemia.
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.
authors.affiliation: Department of Medicine I, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: Anna
authors.initials: A
authors.lastname: Rommer
authors.forename: Katarina
authors.initials: K
authors.lastname: Steinleitner
authors.forename: Hubert
authors.initials: H
authors.lastname: Hackl
authors.forename: Christine
authors.initials: C
authors.lastname: Schneckenleithner
authors.forename: Maria
authors.initials: M
authors.lastname: Engelmann
authors.forename: Marcel
authors.initials: M
authors.lastname: Scheideler
authors.forename: Irena
authors.initials: I
authors.lastname: Vlatkovic
authors.forename: Robert
authors.initials: R
authors.lastname: Kralovics
authors.forename: Sabine
authors.initials: S
authors.lastname: Cerny-Reiterer
authors.forename: Peter
authors.initials: P
authors.lastname: Valent
authors.forename: Heinz
authors.initials: H
authors.lastname: Sill
authors.forename: Rotraud
authors.initials: R
authors.lastname: Wieser
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D055815:Young Adult
chemical_list: D035683:MicroRNAs; C525709:MIR221, human; C525710:MIR222, human
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