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. 2008 May 14;3(5):e2141.
doi: 10.1371/journal.pone.0002141.

Distinctive patterns of microRNA expression associated with karyotype in acute myeloid leukaemia

Amanda Dixon-McIver  1 , Phil East, Charles A Mein, Jean-Baptiste Cazier, Gael Molloy, Tracy Chaplin, T Andrew Lister, Bryan D Young, Silvana Debernardi
Affiliations

Distinctive patterns of microRNA expression associated with karyotype in acute myeloid leukaemia

Amanda Dixon-McIver et al. PLoS One. .

Abstract

Acute myeloid leukaemia (AML) is the most common acute leukaemia in adults; however, the genetic aetiology of the disease is not yet fully understood. A quantitative expression profile analysis of 157 mature miRNAs was performed on 100 AML patients representing the spectrum of known karyotypes common in AML. The principle observation reported here is that AMLs bearing a t(15;17) translocation had a distinctive signature throughout the whole set of genes, including the up regulation of a subset of miRNAs located in the human 14q32 imprinted domain. The set included miR-127, miR-154, miR-154*, miR-299, miR-323, miR-368, and miR-370. Furthermore, specific subsets of miRNAs were identified that provided molecular signatures characteristic of the major translocation-mediated gene fusion events in AML. Analysis of variance showed the significant deregulation of 33 miRNAs across the leukaemic set with respect to bone marrow from healthy donors. Fluorescent in situ hybridisation analysis using miRNA-specific locked nucleic acid (LNA) probes on cryopreserved patient cells confirmed the results obtained by real-time PCR. This study, conducted on about a fifth of the miRNAs currently reported in the Sanger database (microrna.sanger.ac.uk), demonstrates the potential for using miRNA expression to sub-classify cancer and suggests a role in the aetiology of leukaemia.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Unsupervised hierarchical cluster analysis of 123 miRNA expression profiles for 102 leukaemia samples.
Each column represents a sample, and each row represents a single miRNA. The colour display encodes the logarithm of the expression changes, where varying shades of red and green indicate up and down regulation, respectively. Values ranged from log2 (−10) to log2(+10). MiRNAs passing a 5% FDR threshold from the leukaemia versus normal bone marrow comparison are highlighted in red or green on the left of the heatmap. Karyotype labels are also indicated on the top of the heatmap. The colour-key for the labelling is on the top left.
Figure 2
Figure 2. MiRNA detection in cryopreserved bone marrow cells by LNA-FISH.
Patients n. 109 (lanes 1–3) and n. 111 (lanes 4–6) carrying the t(15;17) and t(9;22) translocations, respectively, are shown. All images were obtained with the confocal microscope as described in the method. The DAPI nuclear staining (blue), the fluorescent in situ hybridisation signals obtained with FITC-conjugated antibody (green), and the combined images are indicated. The A and B panels show the detection of miR-127 and miR-154, respectively. Both miRNAs are detected in the cytoplasm of cells (lanes 2 and 3) of patient n. 109 but not in patient n. 111 (lanes 5 and 6). The C panel shows the nuclear expression of U6, the small RNA used as positive control, in both samples (lanes 2 and 5). No signal was detected when cells were hybridised with a scrambled oligonucleotide (negative control), as shows in lanes 2 and 5 of the D panel.
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