Volltext-Downloads (blau) und Frontdoor-Views (grau)

The impact of TEL-AML1 (ETV6-RUNX1) expression in precursor B cells and implications for leukaemia using three different genome-wide screening methods

  • The reciprocal translocation t(12;21)(p13;q22), the most common structural genomic alteration in B-cell precursor acute lymphoblastic leukaemia in children, results in a chimeric transcription factor TEL-AML1 (ETV6-RUNX1). We identified directly and indirectly regulated target genes utilizing an inducible TEL-AML1 system derived from the murine pro B-cell line BA/F3 and a monoclonal antibody directed against TEL-AML1. By integration of promoter binding identified with chromatin immunoprecipitation (ChIP)-on-chip, gene expression and protein output through microarray technology and stable labelling of amino acids in cell culture, we identified 217 directly and 118 indirectly regulated targets of the TEL-AML1 fusion protein. Directly, but not indirectly, regulated promoters were enriched in AML1-binding sites. The majority of promoter regions were specific for the fusion protein and not bound by native AML1 or TEL. Comparison with gene expression profiles from TEL-AML1-positive patients identified 56 concordantly misregulated genes with negative effects on proliferation and cellular transport mechanisms and positive effects on cellular migration, and stress responses including immunological responses. In summary, this work for the first time gives a comprehensive insight into how TEL-AML1 expression may directly and indirectly contribute to alter cells to become prone for leukemic transformation.

Download full text files

Export metadata

Additional Services

Share in Twitter Search Google Scholar Check availability

Statistics

Show usage statistics
Metadaten
Document Type:Article
Language:English
Author:Y. Linka, S. Ginzel, M. Krüger, A. Novosel, M. Gombert, E. Kremmer, J. Harbott, R. Thiele, A. Borkhardt, P. Landgraf
Parent Title (English):Blood Cancer Journal
Volume:3
First Page:e151
ISSN:2044-5385
URN:urn:nbn:de:hbz:1044-opus-10394
DOI:https://doi.org/10.1038/bcj.2013.48
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=24121163
Publisher:Macmillan Publishers
Place of publication:London
Publishing Institution:Hochschule Bonn-Rhein-Sieg
Date of first publication:2013/10/11
Note:
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.
Departments, institutes and facilities:Fachbereich Informatik
Institut für funktionale Gen-Analytik (IFGA)
Dewey Decimal Classification (DDC):6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Entry in this database:2015/04/02
Licence (German):License LogoCreative Commons - CC BY-NC-SA - Namensnennung-Keine kommerzielle Nutzung-Weitergabe unter gleichen Bedingungen 3.0