miR-21 is overexpressed in NPM1-mutant acute myeloid leukemias

Roberta Riccioni; Valentina Lulli; Germana Castelli; Mauro Biffoni; Rosella Tiberio; Elvira Pelosi; Francesco Lo-Coco; Ugo Testa

doi:10.1016/j.leukres.2014.11.001

miR-21 is overexpressed in NPM1-mutant acute myeloid leukemias

Leuk Res. 2015 Feb;39(2):221-8. doi: 10.1016/j.leukres.2014.11.001. Epub 2014 Nov 18.

Authors

Roberta Riccioni¹, Valentina Lulli¹, Germana Castelli¹, Mauro Biffoni¹, Rosella Tiberio², Elvira Pelosi¹, Francesco Lo-Coco³, Ugo Testa⁴

Affiliations

¹ Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
² SIMT Ospedale San Pietro FBF, Via Cassia, Rome, Italy.
³ Department of Biopathology, University of Tor Vergata and Laboratorio of Neuro-Oncoematologia, Fondazione Santa Lucia, Rome, Italy.
⁴ Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy. Electronic address: ugo.testa@iss.it.

PMID: 25543261
DOI: 10.1016/j.leukres.2014.11.001

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.

Keywords: Acute myeloid leukemia; Cell differentiation; Leukemia; Membrane antigens; MicroRNA.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis Regulatory Proteins / genetics
Apoptosis Regulatory Proteins / metabolism
Female
Gene Expression Regulation, Leukemic*
Humans
Leukemia, Myeloid, Acute* / genetics
Leukemia, Myeloid, Acute* / metabolism
Leukemia, Myeloid, Acute* / pathology
Male
MicroRNAs / biosynthesis*
MicroRNAs / genetics
Mutation*
Neoplasm Proteins / genetics*
Neoplasm Proteins / metabolism
Nuclear Proteins / genetics*
Nuclear Proteins / metabolism
Nucleophosmin
RNA, Neoplasm / biosynthesis*
RNA, Neoplasm / genetics
RNA-Binding Proteins / genetics
RNA-Binding Proteins / metabolism

Substances

Apoptosis Regulatory Proteins
MIRN21 microRNA, human
MicroRNAs
NPM1 protein, human
Neoplasm Proteins
Nuclear Proteins
PDCD4 protein, human
RNA, Neoplasm
RNA-Binding Proteins
Nucleophosmin