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


RESULTS
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.
Laboratory of Neuro-Oncohematology, Santa Lucia Foundation, Rome, Italy. faraoni@med.uniroma2.it
Isabella
I
Faraoni
Serena
S
Laterza
Davide
D
Ardiri
Claudia
C
Ciardi
Francesco
F
Fazi
Francesco
F
Lo-Coco
D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics; D016022:Case-Control Studies; D020869:Gene Expression Profiling; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
D014408:Biomarkers, Tumor; C524942:MIRN155 microRNA, human; C554214:MIRN424 microrna, human; D035683:MicroRNAs; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3