John Libbey Eurotext



MicroRNA and haematology Volume 14, issue 2, mars-avril 2008


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Département d’hématologie clinique, Centre Henri-Becquerel, Rouen, INSERM U918, IFR23, Centre Henri-Becquerel, Rouen

MicroRNA (MiRNA) are non-coding single-stranded RNAs of 21-25 nucleotides and constitute a novel class of gene regulators that inhibits their targets by base pair complementarity. 20-30% of genes are supposed to be regulated by miRNA and each miRNA control an average of two hundred target genes. They are involved in various biological processes such as cell differentiation, cell cycle or apoptosis. MiRNA are implicated in normal hematopoiesis mainly by repressing key genes involved during differentiation. MiR-181 and miR-128 inhibit differentiation of all haematopoietic lineages. MiR-221/miR-222 and miR-223 act only during erythroid and granulocytic development respectively. MiR-155 expression is crucial during normal B and T-cell development. MiRNA have a broad impact during oncogenesis and can function as tumor suppressors or oncogenes. Genomic alterations leading to deregulation of miRNA expression include deletions, gene amplifications, point mutations, epigenic changes (methylation) or promoter substitution. High expression of miR-155 or miR-17-92 are observed in various lymphoma subtypes. Mouse model expressing the Eμ/miR-155 transgene suggests that miR-155 may be implicated during the early steps of lymphomagenesis. Deletion or point mutations of miR-15a/miR-16-1, an antiapoptotic BCL2 protein regulator, are observed in more than 50% of cases and notably in familial forms. MiRNA expression profiling in acute leukemia indicates that miRNA expression reflects mechanisms of transformation. Molecular diagnosis and classification of haematological malignancies, predictive genomics, and pharmacogenomics represent promising area of developments. Furthermore, because miRNA can simultaneously modulate the expression of multiple genes, they are potential effective targets for cancer therapy. MiRNA silencing by antisens molecules or modulation of their expression by epigenetic treatment may be novel strategies for anticancer therapy.