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Abstract

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-1β.

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.

Details

Title
MicroRNA Expression in Cytogenetically Normal Acute Myeloid Leukemia
Author
Marcucci, Guido, MD; Radmacher, Michael D, PhD; Maharry, Kati, MAS; Mrózek, Krzysztof, MD, PhD; Ruppert, Amy S, MAS; Paschka, Peter, MD; Vukosavljevic, Tamara, BS; Whitman, Susan P, PhD; Baldus, Claudia D, MD; Langer, Christian, MD; Liu, Chang-Gong, PhD; Carroll, Andrew J, PhD; Powell, Bayard L, MD; Garzon, Ramiro, MD; Croce, Carlo M, MD; Kolitz, Jonathan E, MD; Caligiuri, Michael A, MD; Larson, Richard A, MD; Bloomfield, Clara D, MD
Pages
1919-28
Section
16; 25; Original Article
Publication year
2008
Publication date
May 1, 2008
Publisher
Massachusetts Medical Society
ISSN
00284793
e-ISSN
15334406
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
223931956
Copyright
Copyright © 2008 Massachusetts Medical Society. All rights reserved.