MiR-424 and miR-155 deregulated expression in cytogenetically normal acute myeloid leukaemia: correlation with NPM1 and FLT3 mutation status

J Hematol Oncol. 2012 Jun 8:5:26. doi: 10.1186/1756-8722-5-26.

Abstract

Background: MicroRNA have a central role in normal haematopoiesis and are deregulated in acute myeloid leukaemia (AML). The purpose of the study was to investigate by qRT-PCR the expression of miRNAs involved in myeloid differentiation (miR-424, miR-155, miR-223, miR-17-5p) in 48 patients with cytogenetically normal AML well characterized for NPM1 and/or FLT3 mutations. Three types of normalization were used for the data validation.

Findings: We found that miR-424 was down-modulated in AMLs with NPM1mutA regardless of FLT3 status. On the contrary, miR-155 showed up-regulation in patients with FLT3 internal tandem duplications (ITD) with or without NPM1 mutations. No significant associations were found by analyzing miR-223 and miR-17-5p in relation to FLT3 and NPM1 status.

Conclusions: This study supports the view that major genetic subsets of CN-AML are associated with distinct miRNA signatures and suggests that miR-424 and miR-155 deregulation is involved in the pathogenesis of CN-AML with NPM1 and FLT3-ITD mutations, respectively.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers, Tumor / genetics
  • Case-Control Studies
  • Gene Expression Profiling
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / pathology
  • MicroRNAs / genetics*
  • Mutation / genetics*
  • Nuclear Proteins / genetics*
  • Nucleophosmin
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation
  • fms-Like Tyrosine Kinase 3 / genetics*

Substances

  • Biomarkers, Tumor
  • MIRN155 microRNA, human
  • MIRN424 microrna, human
  • MicroRNAs
  • NPM1 protein, human
  • Nuclear Proteins
  • RNA, Messenger
  • Nucleophosmin
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3