title: Differential expression of specific microRNA and their targets in acute myeloid leukemia.
abstract: Acute myeloid leukemia (AML) the most common acute leukemia in adults is characterized by various cytogenetic and molecular abnormalities. However, the genetic etiology of the disease is not yet fully understood. MicroRNAs (miRNA) are small noncoding RNAs which regulate the expression of target mRNAs both at transcriptional and translational level. In recent years, miRNAs have been identified as a novel mechanism in gene regulation, which show variable expression during myeloid differentiation. We studied miRNA expression of leukemic blasts of 29 cases of newly diagnosed and genetically defined AML using quantitative reverse transcription polymerase chain reaction (RT-PCR) for 365 human miRNA. We showed that miRNA expression profiling reveals distinctive miRNA signatures that correlate with cytogenetic and molecular subtypes of AML. Specific miRNAs with consolidated role on cell proliferation and differentiation such as miR-155, miR-221, let-7, miR-126 and miR-196b appear to be associated with particular subtypes. We observed a significant differentially expressed miRNA profile that characterizes two subgroups of AML with different mechanism of leukemogenesis: core binding factor (CBF) and cytogenetically normal AML with mutations in the genes of NPM1 and FLT3-ITD. We demonstrated, for the first time, the inverse correlation of expression levels between miRNA and their targets in specific AML genetic groups. We suggest that miRNA deregulation may act as complementary hit in the multisteps mechanism of leukemogenesis offering new therapeutic strategies.
authors.affiliation: Divisione di Ematologia con UTMO, A.O. Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cammarata
authors.forename: Luigi
authors.initials: L
authors.lastname: Augugliaro
authors.forename: Domenico
authors.initials: D
authors.lastname: Salemi
authors.forename: Cecilia
authors.initials: C
authors.lastname: Agueli
authors.forename: Maria
authors.initials: M
authors.lastname: La Rosa
authors.forename: Lea
authors.initials: L
authors.lastname: Dagnino
authors.forename: Gabriele
authors.initials: G
authors.lastname: Civiletto
authors.forename: Francesca
authors.initials: F
authors.lastname: Messana
authors.forename: Anna
authors.initials: A
authors.lastname: Marfia
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Bica
authors.forename: Lucia
authors.initials: L
authors.lastname: Cascio
authors.forename: Pietro Michele
authors.initials: PM
authors.lastname: Floridia
authors.forename: Angelo M
authors.initials: AM
authors.lastname: Mineo
authors.forename: Mario
authors.initials: M
authors.lastname: Russo
authors.forename: Francesco
authors.initials: F
authors.lastname: Fabbiano
authors.forename: Alessandra
authors.initials: A
authors.lastname: Santoro
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation; D050660:Core Binding Factors / Q000502:physiology; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D042381:Granulocyte Precursor Cells / Q000378:metabolism*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000145:classification / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: D050660:Core Binding Factors; D035683:MicroRNAs; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3