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Differential expression of specific microRNA and their targets in acute myeloid leukemia
Author(s) -
Cammarata Giuseppe,
Augugliaro Luigi,
Salemi Domenico,
Agueli Cecilia,
Rosa Maria La,
Dagnino Lea,
Civiletto Gabriele,
Messana Francesca,
Marfia Anna,
Bica Maria Grazia,
Cascio Lucia,
Floridia Pietro Michele,
Mineo Angelo M.,
Russo Mario,
Fabbiano Francesco,
Santoro Alessandra
Publication year - 2010
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.21667
Subject(s) - microrna , myeloid leukemia , biology , npm1 , myeloid , leukemia , gene , cancer research , transcription factor , gene expression , gene expression profiling , genetics , karyotype , chromosome
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. Am. J. Hematol. 2010. © 2010 Wiley‐Liss, Inc.