Che-1 is targeted by c-Myc to sustain proliferation in pre-B-cell acute lymphoblastic leukemia
| Autor: | Folgiero, V, and Sorino, C, and Pallocca, M, and De Nicola, F, and Goeman, F, and Bertaina, V, and Strocchio, L, Romania, P, and Pitisci, A, and Iezzi, S, And, Catena, V, and Bruno, T, and Strimpakos, G, And, Passananti, C, and Mattei, E, and Blandino, G, And, Locatelli, F and Fanciulli, M. |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Disease onset BCP-ALL Lymphoblastic Leukemia proliferation Disease che‐1 Biochemistry leukemogenesis Treatment failure Proto-Oncogene Proteins c-myc 03 medical and health sciences chemistry.chemical_compound RNA polymerase Cell Line Tumor Precursor B-Cell Lymphoblastic Leukemia-Lymphoma Genetics Medicine Humans Promoter Regions Genetic Molecular Biology Cell Proliferation business.industry Effector Gene Expression Regulation Leukemic High-Throughput Nucleotide Sequencing Pre B-cell acute lymphoblastic leukemia Articles Precursor Cell Lymphoblastic Leukemia-Lymphoma DNA-Binding Proteins Repressor Proteins 030104 developmental biology c-Myc Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA bcp‐ALL c‐Myc chemistry Che-1 Direct binding Cancer research Neoplasm Recurrence Local business Apoptosis Regulatory Proteins |
| Zdroj: | EMBO reports Volume 19 (2018). doi:10.15252/embr.201744871 info:cnr-pdr/source/autori:Folgiero V, Sorino C, Pallocca M, De Nicola F, Goeman F, Bertaina V, Strocchio L, Romania P, Pitisci A, Iezzi S, Catena V, Bruno T, Strimpakos G, Passananti C, Mattei E, Blandino G, Locatelli F, Fanciulli M./titolo:Che-1 is targeted by c-Myc to sustain proliferation in pre-B-cell acute lymphoblastic leukemia/doi:10.15252%2Fembr.201744871/rivista:EMBO reports (Print)/anno:2018/pagina_da:/pagina_a:/intervallo_pagine:/volume:Volume 19 |
| DOI: | 10.15252/embr.201744871 |
| Popis: | Despite progress in treating B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL), disease recurrence remains the main cause of treatment failure. New strategies to improve therapeutic outcomes are needed, particularly in high‐risk relapsed patients. Che‐1/AATF (Che‐1) is an RNA polymerase II‐binding protein involved in proliferation and tumor survival, but its role in hematological malignancies has not been clarified. Here, we show that Che‐1 is overexpressed in pediatric BCP‐ALL during disease onset and at relapse, and that its depletion inhibits the proliferation of BCP‐ALL cells. Furthermore, we report that c‐Myc regulates Che‐1 expression by direct binding to its promoter and describe a strict correlation between Che‐1 expression and c‐Myc expression. RNA‐seq analyses upon Che‐1 or c‐Myc depletion reveal a strong overlap of the respective controlled pathways. Genomewide ChIP‐seq experiments suggest that Che‐1 acts as a downstream effector of c‐Myc. These results identify the pivotal role of Che‐1 in the control of BCP‐ALL proliferation and present the protein as a possible therapeutic target in children with relapsed BCP‐ALL. |
| Databáze: | OpenAIRE |
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