MicroRNA expression in cytogenetically normal acute myeloid leukemia.| Authors: | Guido Marcucci, Michael D Radmacher, Kati Maharry, Krzysztof Mrózek, Amy S Ruppert, Peter Paschka, Tamara Vukosavljevic, Susan P Whitman, Claudia D Baldus, Christian Langer, Chang-Gong Liu, Andrew J Carroll, Bayard L Powell, Ramiro Garzon, Carlo M Croce, Jonathan E Kolitz, Michael A Caligiuri, Richard A Larson, Clara D Bloomfield | | Language: | Eng. | | Date: | 02-05-2008 | | Journal: | The New England journal of medicine
(1533-4406)
| | Release: | N Engl J Med. 2008 May;358(18):1919-28 | |
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Abstract:
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BACKGROUND:
A role of microRNAs in cancer has recently been recognized. However, little is known about the role of microRNAs in acute myeloid leukemia (AML).
METHODS:
Using microRNA expression profiling, we studied samples of leukemia cells from adults under the age of 60 years who had cytogenetically normal AML and high-risk molecular features--that is, an internal tandem duplication in the fms-related tyrosine kinase 3 gene (FLT3-ITD), a wild-type nucleophosmin (NPM1), or both. A microRNA signature that was associated with event-free survival was derived from a training group of 64 patients and tested in a validation group of 55 patients. For the latter, a microRNA compound covariate predictor (called a microRNA summary value) was computed on the basis of weighted levels of the microRNAs forming the outcome signature.
RESULTS:
Of 305 microRNA probes, 12 (including 5 representing microRNA-181 family members) were associated with event-free survival in the training group (P<0.005). In the validation group, the microRNA summary value was inversely associated with event-free survival (P=0.03). In multivariable analysis, the microRNA summary value remained associated with event-free survival (P=0.04) after adjustment for the allelic ratio of FLT3-ITD to wild-type FLT3 and for the white-cell count. Using results of gene-expression microarray analysis, we found that expression levels of the microRNA-181 family were inversely correlated with expression levels of predicted target genes encoding proteins involved in pathways of innate immunity mediated by toll-like receptors and interleukin-1beta.
CONCLUSIONS:
A microRNA signature in molecularly defined, high-risk, cytogenetically normal AML is associated with the clinical outcome and with target genes encoding proteins involved in specific innate-immunity pathways.
| | Copyright: | The New England journal of medicine
Division of Hematology and Oncology, Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USA. guido.marcucci@osumc.edu | | Full text: | | | Terms: | Adult, Analysis of Variance, DNA-Binding Proteins, Female, Gene Expression, Gene Expression Profiling, Gene Expression Regulation, Leukemic, Genetic Markers, Genetic Predisposition to Disease, Humans, Kaplan-Meiers Estimate, Leukemia, Myeloid, Acute, MicroRNAs, Middle Aged, Mutation, Nuclear Proteins, Oligonucleotide Array Sequence Analysis, Prognosis, Proportional Hazards Models, RNA Probes, RNA, Neoplasm, Trans-Activators, fms-Like Tyrosine Kinase 3 | | |
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