Article (Scientific journals)
Predicting interactome networks perturbations in human cancer: application to gene fusions in acute lymphoblastic leukemia.
Juvenal Hajingabo, Leon; Daakour, Sarah; Martin, Maud et al.
2014In Molecular Biology of the Cell
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Abstract :
[en] Genomic variations such as point mutations and gene fusions are directly or indirectly associated with human diseases. They are recognized as diagnostic, prognostic markers and therapeutic targets. However, predicting the functional impact of these genetic alterations beyond affected genes and their products is challenging because diseased phenotypes are likely dependent of complex molecular interaction networks. Using as models three different chromosomal translocations ETV6-RUNX1 (TEL-AML1), BCR-ABL1, and TCF3-PBX1 (E2A-PBX1), frequently found in precursor-B cell acute lymphoblastic leukemia (preB-ALL), we develop an approach to extract perturbed molecular interactions from gene expression changes. We show that the MYC and JunD transcriptional circuits are specifically deregulated following ETV6-RUNX1 and TCF3-PBX1 gene fusions, respectively. We also identified the bulk mRNA NXF1-dependent machinery as a direct target for the TCF3-PBX1 fusion protein. Through a novel approach combining gene expression and interactome data analysis, we provide new insight into TCF3-PBX1 and ETV6-RUNX1 acute lymphoblastic leukemia.
Research center :
Protein Signaling and Interactions GIGA -Siganaling transduction
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Juvenal Hajingabo, Leon
Daakour, Sarah ;  Université de Liège - ULiège > Chimie et bio-industries > Biologie cell. et moléc.
Martin, Maud ;  Université de Liège - ULiège > Chimie et bio-industries > Biologie cell. et moléc.
Grausenburger, Reinhard
Panzer-Grumayer, Renate
Dequiedt, Franck  ;  Université de Liège - ULiège > GIGA-Research
Simonis, Nicolas
Twizere, Jean-Claude  ;  Université de Liège - ULiège > GIGA -Siganaling Transduction > Protein Signaling and Interactions > Principal Investigator
Language :
English
Title :
Predicting interactome networks perturbations in human cancer: application to gene fusions in acute lymphoblastic leukemia.
Publication date :
2014
Journal title :
Molecular Biology of the Cell
ISSN :
1059-1524
eISSN :
1939-4586
Publisher :
American Society for Cell Biology, United States - Maryland
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
Perturbations of interactome network in acute lymphoblastic leukemia
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Commentary :
(c) 2014 by The American Society for Cell Biology.
Available on ORBi :
since 20 December 2014

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