title: MYCN is a novel oncogenic target in pediatric T-cell acute lymphoblastic leukemia.
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.
authors: "Giorgio Prodi" Cancer Research Center, University of Bologna, Bologna, Italy.
authors: Annalisa
authors: A
authors: Astolfi
authors: Francesca
authors: F
authors: Vendemini
authors: Milena
authors: M
authors: Urbini
authors: Fraia
authors: F
authors: Melchionda
authors: Riccardo
authors: R
authors: Masetti
authors: Monica
authors: M
authors: Franzoni
authors: Virginia
authors: V
authors: Libri
authors: Salvatore
authors: S
authors: Serravalle
authors: Marco
authors: M
authors: Togni
authors: Giuseppina
authors: G
authors: Paone
authors: Luca
authors: L
authors: Montemurro
authors: Daniela
authors: D
authors: Bressanin
authors: Francesca
authors: F
authors: Chiarini
authors: Alberto M
authors: AM
authors: Martelli
authors: Roberto
authors: R
authors: Tonelli
authors: Andrea
authors: A
authors: Pession
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D005260:Female; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection; D016896:Treatment Outcome
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C459801:MYCN protein, human; C067143:TAL1 protein, human