title: A restricted signature of miRNAs distinguishes APL blasts from normal promyelocytes.
abstract: MicroRNAs (miRNAs) are small non-coding RNAs involved in the regulation of critical cell processes such as apoptosis, cell proliferation and differentiation. A small set of miRNAs is differentially expressed in hematopoietic cells and seemingly has an important role in granulopoiesis and lineage differentiation. In this study, we analysed, using a quantitative real-time PCR approach, the expression of 12 granulocytic differentiation signature miRNAs in a cohort of acute promyelocytic leukemia (APL) patients. We found nine miRNAs overexpressed and three miRNAs (miR-107, -342 and let-7c) downregulated in APL blasts as compared with normal promyelocytes differentiated in vitro from CD34+ progenitors. Patients successfully treated with all-trans-retinoic acid (ATRA) and chemotherapy showed downregulation of miR-181b and upregulation of miR-15b, -16, -107, -223, -342 and let-7c. We further investigated whether the APL-associated oncogene, promyelocytic leukemia gene (PML)/retinoic acid receptor alpha (RARalpha), might be involved in the transcriptional repression of miR-107, -342 and let-7c. We found that PML/RARalpha binds the regulatory sequences of the intragenic miR-342 and let-7c. In addition, we observed, in response to ATRA, the release of PML/RARalpha paralleled by their transcriptional activation, together with their host genes, EVL and C21orf34alpha. In conclusion, we show that a small subset of miRNAs is differentially expressed in APL and modulated by ATRA-based treatment.
authors.affiliation: Laboratory of Molecular Oncogenesis, Department of Experimental Oncology, Regina Elena Cancer Institute, Rome 00158, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Careccia
authors.forename: S
authors.initials: S
authors.lastname: Mainardi
authors.forename: A
authors.initials: A
authors.lastname: Pelosi
authors.forename: A
authors.initials: A
authors.lastname: Gurtner
authors.forename: D
authors.initials: D
authors.lastname: Diverio
authors.forename: R
authors.initials: R
authors.lastname: Riccioni
authors.forename: U
authors.initials: U
authors.lastname: Testa
authors.forename: E
authors.initials: E
authors.lastname: Pelosi
authors.forename: G
authors.initials: G
authors.lastname: Piaggio
authors.forename: A
authors.initials: A
authors.lastname: Sacchi
authors.forename: S
authors.initials: S
authors.lastname: Lavorgna
authors.forename: F
authors.initials: F
authors.lastname: Lo-Coco
authors.forename: G
authors.initials: G
authors.lastname: Blandino
authors.forename: M
authors.initials: M
authors.lastname: Levrero
authors.forename: M G
authors.initials: MG
authors.lastname: Rizzo
mesh_terms: D042381:Granulocyte Precursor Cells / Q000473:pathology; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000032:analysis* / Q000235:genetics
chemical_list: D035683:MicroRNAs