The prognostic and functional role of microRNAs in acute myeloid leukemia.
Expression of microRNAs, a new class of noncoding RNAs that hybridize to target messenger RNA and regulate their translation into proteins, has been recently demonstrated to be altered in acute myeloid leukemia (AML). Distinctive patterns of increased expression and/or silencing of multiple microRNAs (microRNA signatures) have been associated with specific cytogenetic and molecular subsets of AML. Changes in the expression of several microRNAs altered in AML have been shown to have functional relevance in leukemogenesis, with some microRNAs acting as oncogenes and others as tumor suppressors. Both microRNA signatures and a single microRNA (ie, miR-181a) have been shown to supply prognostic information complementing that gained from cytogenetics, gene mutations, and altered gene expression. Moreover, it has been demonstrated experimentally that antileukemic effects can be achieved by modulating microRNA expression by pharmacologic agents and/or increasing low endogenous levels of microRNAs with tumor suppressor function by synthetic microRNA oligonucleotides, or down-regulating high endogenous levels of leukemogenic microRNAs by antisense oligonucleotides (antagomirs). Therefore, it is reasonable to predict the development of novel microRNA-based therapeutic approaches in AML. We review herein results of current studies analyzing changes of microRNA expression in AML and discuss their potential biologic, diagnostic, and prognostic relevance.
Division of Hematology, Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University, 460 West 12th Avenue, Columbus, OH 43210, USA. guido.marcucci@osumc.edu
Guido
G
Marcucci
Krzysztof
K
Mrózek
Michael D
MD
Radmacher
Ramiro
R
Garzon
Clara D
CD
Bloomfield
D020732:Cytogenetic Analysis; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics* / Q000502:physiology*
D035683:MicroRNAs