Distinctive patterns of microRNA expression associated with karyotype in acute myeloid leukaemia.
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.
Dixon-McIver
Amanda
A
Institute of Cancer, Medical Oncology Centre, Barts and The London, School Of Medicine, London, United Kingdom.
East
Phil
P
Mein
Charles A
CA
Cazier
Jean-Baptiste
JB
Molloy
Gael
G
Chaplin
Tracy
T
Andrew Lister
T
T
Young
Bryan D
BD
Debernardi
Silvana
S
D000704:Analysis of Variance; D001483:Base Sequence; D002869:Chromosome Aberrations; D002883:Chromosomes, Human, Pair 14; D015342:DNA Probes; D020869:Gene Expression Profiling; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D009841:Oligonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction
D015342:DNA Probes; D035683:MicroRNAs; D009841:Oligonucleotides; C477371:locked nucleic acid