title: miR-21 is overexpressed in NPM1-mutant acute myeloid leukemias.
abstract: MicroRNAs (miRs) play a key role in the pathogenesis of human malignancies and particularly in acute myeloid leukemias (AMLs) and are increasingly recognized as potential biomarkers and therapeutic targets. miR-21 is dysregulated in several types of cancers, including some hematologic malignancies, and plays a key role in carcinogenesis, disease recurrence and metastasis. However, no studies have specifically investigated the role of miR-21 in AMLs. In this study we analyzed the expression of miR-21 and of its target PDCD4 (Programmed Cell Death 4) during normal hematopoietic differentiation and in AMLs. Our results showed that: (i) miR-21 expression is strongly up-modulated during normal granulo/monocytic differentiation, while PDCD4 protein level is concomitantly downmodulated; (ii) miR-21 is frequently overexpressed in AML blasts, in association with a marked PDCD4 protein downmodulation; (iii) miR-21 expression level is particularly elevated in NPM1mutant AMLs. Together, these findings suggest that deregulated miR-21 expression may contribute to disease pathogenesis in NPM1-mutated AMLs.
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Riccioni
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Lulli
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Germana
authors.initials: G
authors.lastname: Castelli
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Biffoni
authors.affiliation: SIMT Ospedale San Pietro FBF, Via Cassia, Rome, Italy.
authors.forename: Rosella
authors.initials: R
authors.lastname: Tiberio
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Elvira
authors.initials: E
authors.lastname: Pelosi
authors.affiliation: Department of Biopathology, University of Tor Vergata and Laboratorio of Neuro-Oncoematologia, Fondazione Santa Lucia, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Lo-Coco
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy. Electronic address: ugo.testa@iss.it.
authors.forename: Ugo
authors.initials: U
authors.lastname: Testa
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D000090243:Nucleophosmin; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C000716967:NPM1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C114487:PDCD4 protein, human; D012334:RNA, Neoplasm; D016601:RNA-Binding Proteins; D000090243:Nucleophosmin
keywords: Acute myeloid leukemia; Cell differentiation; Leukemia; Membrane antigens; MicroRNA