MYCN is a Novel Oncogenic Target in Pediatric T-cell Acute Lymphoblastic Leukemia

Overview

Journal Oncotarget

Specialty Oncology

Date 2013 Dec 17

PMID 24334727

Citations 21

Authors

Annalisa Astolfi

Francesca Vendemini

Milena Urbini

Fraia Melchionda

Riccardo Masetti

Monica Franzoni

Virginia Libri

Salvatore Serravalle

Marco Togni

Giuseppina Paone

Luca Montemurro

Daniela Bressanin

Francesca Chiarini

Alberto M Martelli

Roberto Tonelli

Andrea Pession

Affiliations

Soon will be listed here.

Abstract

MYCN is an oncogene frequently overexpressed in pediatric solid tumors whereas few evidences suggest his involvement in the pathogenesis of haematologic malignancies. Here we show that MYCN is overexpressed in a relevant proportion (40 to 50%) of adult and pediatric T-cell acute lymphoblastic leukemias (T-ALL). Focusing on pediatric T-ALL, MYCN-expressing samples were found almost exclusively in the TAL1-positive subgroup. Moreover, TAL1 knockdown in T-ALL cell lines resulted in a reduction of MYCN expression, and TAL1 directly binds to MYCN promoter region, suggesting that TAL1 pathway activation could sustain the up-regulation of MYCN. The role of MYCN in T-ALL was investigated by peptide nucleic acid (PNA-MYCN)-mediated transcriptional silencing of MYCN and by siRNAs. MYCN knockdown in T-ALL cell lines resulted in a reduction of cell viability, up to 50%, while no effect was elicited with a mismatch PNA. The inhibitory effect of PNA-MYCN on cell viability was due to a significant increase in apoptosis. PNA-MYCN treatment in pediatric T-ALL samples reduced cell viability of leukemic cells from patients with high MYCN expression, while no effect was obtained in MYCN-negative blast cells. These results showed that MYCN is frequently overexpressed in pediatric T-ALL and suggested his role as a candidate for molecularly-directed therapies.

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