MicroRNA expression in cytogenetically normal acute myeloid leukemia

Academic Article

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. Copyright © 2008 Massachusetts Medical Society.
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    Digital Object Identifier (doi)

    Author List

  • Marcucci G; Radmacher MD; Maharry K; Mrózek K; Ruppert AS; Paschka P; Vukosavljevic T; Whitman SP; Baldus CD; Langer C
  • Start Page

  • 1919
  • End Page

  • 1928
  • Volume

  • 358
  • Issue

  • 18