Integrative analysis of RUNX1 downstream pathways and target genes

ResearchWorks/Manakin Repository

Search ResearchWorks


Advanced Search

Browse

My Account

Statistics

Related Information

Integrative analysis of RUNX1 downstream pathways and target genes

Show simple item record

dc.contributor.author Michaud, Joelle en_US
dc.contributor.author Simpson, Ken M. en_US
dc.contributor.author Escher, Robert en_US
dc.contributor.author Buchet-Poyau, Karine en_US
dc.contributor.author Beissbarth, Tim en_US
dc.contributor.author Carmichael, Catherine en_US
dc.contributor.author Ritchie, Matthew E. en_US
dc.contributor.author Schutz, Frederic en_US
dc.contributor.author Cannon, Ping en_US
dc.contributor.author Liu, Marjorie en_US
dc.contributor.author Shen, Xiaofeng en_US
dc.contributor.author Ito, Yoshiaki en_US
dc.contributor.author Raskind, Wendy H. en_US
dc.contributor.author Horwitz, Marshall S. en_US
dc.contributor.author Osato, Motomi en_US
dc.contributor.author Turner, David R. en_US
dc.contributor.author Speed, Terence P. en_US
dc.contributor.author Kavallaris, Maria en_US
dc.contributor.author Smyth, Gordon K. en_US
dc.contributor.author Scott, Hamish S. en_US
dc.date.accessioned 2010-05-06T20:04:43Z
dc.date.available 2010-05-06T20:04:43Z
dc.date.issued 2008 en_US
dc.identifier.citation Michaud J, Simpson K, Escher R, et al. Integrative analysis of RUNX1 downstream pathways and target genes. BMC Genomics. 2008;9(1):363. en_US
dc.identifier.other 10.1186/1471-2164-9-363 en_US
dc.identifier.uri http://www.biomedcentral.com/1471-2164/9/363 en_US
dc.identifier.uri http://hdl.handle.net/1773/15832
dc.description.abstract Background: The RUNX1 transcription factor gene is frequently mutated in sporadic myeloid and lymphoid leukemia through translocation, point mutation or amplification. It is also responsible for a familial platelet disorder with predisposition to acute myeloid leukemia (FPD-AML). The disruption of the largely unknown biological pathways controlled by RUNX1 is likely to be responsible for the development of leukemia. We have used multiple microarray platforms and bioinformatic techniques to help identify these biological pathways to aid in the understanding of why RUNX1 mutations lead to leukemia. Results: Here we report genes regulated either directly or indirectly by RUNX1 based on the study of gene expression profiles generated from 3 different human and mouse platforms. The platforms used were global gene expression profiling of: 1) cell lines with RUNX1 mutations from FPD-AML patients, 2) over-expression of RUNX1 and CBF[Beta], and 3) Runx1 knockout mouse embryos using either cDNA or Affymetrix microarrays. We observe that our datasets (lists of differentially expressed genes) significantly correlate with published microarray data from sporadic AML patients with mutations in either RUNX1 or its cofactor, CBF[Beta]. A number of biological processes were identified among the differentially expressed genes and functional assays suggest that heterozygous RUNX1 point mutations in patients with FPD-AML impair cell proliferation, microtubule dynamics and possibly genetic stability. In addition, analysis of the regulatory regions of the differentially expressed genes has for the first time systematically identified numerous potential novel RUNX1 target genes. Conclusion: This work is the first large-scale study attempting to identify the genetic networks regulated by RUNX1, a master regulator in the development of the hematopoietic system and leukemia. The biological pathways and target genes controlled by RUNX1 will have considerable importance in disease progression in both familial and sporadic leukemia as well as therapeutic implications. en_US
dc.language.iso en_US en_US
dc.title Integrative analysis of RUNX1 downstream pathways and target genes en_US
dc.type Article en_US


Files in this item

Files Size Format View
1471-2164-9-363.pdf 1.474Mb PDF View/Open

This item appears in the following Collection(s)

Show simple item record