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Blood, 15 May 2008, Vol. 111, No. 10, pp. 5078-5085.
Prepublished online as a Blood First Edition Paper on March 12, 2008; DOI 10.1182/blood-2008-01-133355.
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Submitted January 11, 2008
Accepted March 5, 2008
MicroRNA expression profiling in relation to the genetic heterogeneity of acute myeloid leukemia
Mojca Jongen-Lavrencic*, Su Ming Sun, Menno K Dijkstra, Peter JM Valk, and Bob Lowenberg
Department of Hematology, Erasmus University Medical Center, Rotterdam, Netherlands
* Corresponding author; email: m.lavrencic{at}erasmusmc.nl.
Acute myeloid leukemia (AML) is a highly diverse disease characterized by various cytogenetic and molecular abnormalities. MicroRNAs are small non-coding RNAs that show variable expression during myeloid differentiation.
MicroRNAs expression in marrow blasts in 215 cases of newly diagnosed and (cyto)genetically defined AML was assessed using quantitative RT-PCR for 260 known human microRNAs. In the same series mRNA gene expression profiles were established, allowing a direct comparison between microRNA and mRNA expression.
We show that microRNA expression profiling following unsupervised analysis reveals distinctive microRNA signatures that correlate with cytogenetic and molecular subtypes of AML i.e AMLs with t(8;21), t(15;17), inv(16), NPM1 and CEBPA mutations. Significantly differentially expressed microRNAs for genetic subtypes of AML were identified. Specific microRNAs with established oncogenic and tumor suppressor functions, such as microRNA-155, microRNA-21, let-7 appear to be associated with particular subtypes. Combinations of selected sets of microRNAs could predict cytogenetically normal AML with mutations in the genes of NPM1 and CEBPA and FLT3-ITD with similar accuracy as mRNA probe set combinations defined by gene expression profiling (GEP). MicroRNA expression apparently bears specific relationships to the heterogeneous pathobiology of AML. Distinctive microRNA signatures appear of potential value in the clinical diagnosis of AML.

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