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Series GSE22923 Query DataSets for GSE22923
Status Public on May 19, 2011
Title Cell of origin in AML: Susceptibility to MN1-induced transformation is regulated by the MEIS1/abdB-like HOX protein complex
Organism Mus musculus
Experiment type Expression profiling by array
Summary The molecular mechanism defining susceptibility of normal cells to oncogenic transformation may be a valuable therapeutic target. We characterized the cell of origin and its critical pathways in MN1 leukemias. Common myeloid (CMP), but not granulocyte-macrophage progenitors (CMP) could be transformed by constitutively overexpressed MN1. Complementation studies of CMP-signature genes in GMPs demonstrated that leukemogenicity of MN1 required the MEIS1/abdB-like HOX protein complex. Colocalization studies by ChIP-seq identified common chromatin targets of MN1 and MEIS1 that were associated with open chromatin and transcriptional activation. Transcriptional repression of MEIS1 target sites in established MN1 leukemias had antileukemic activity. As MN1 relies on but can not activate expression of MEIS1/abdB-like HOX proteins, transcriptional activity of these genes determines which cell is the cell of origin in MN1 leukemia.
 
Overall design We have showed at the single cell level that CMPs, but not GMPs, are susceptible to MN1-induced transformation. To identify transcriptional differences between CMPs and GMPs that may explain this difference in susceptibilities to MN1 transformation we produced gene expression profiles (two biological replicates in each experimental arm) of bone marrow cells from MN1 leukemic mice and mature myeloid bone marrow cells (Gr1+/CD11b+) from healthy mice and compared those to already published gene expression profiles of CMPs and GMPs (Krivtsov, A.V., et al. (2006). Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9. Nature 442, 818-822).
 
Contributor(s) Heuser M, Yun H, Argiropoulos B, Yung E, Kuchenbauer F, Park G, Hamwi I, Palmqvist L, Lai C, Leung M, Lin G, Iwasaki M, Thiessen N, Robertson G, Hirst M, Kent D, Eaves C, Cleary ML, Marra M, Ganser A, Humphries KR
Citation(s) 21741595
Submission date Jul 13, 2010
Last update date Feb 11, 2019
Contact name Lars Palmqvist
E-mail(s) lars.palmqvist@clinchem.gu.se
Organization name University of Gothenburg
Department Institute of Biomedicine
Lab Department of Laboratory Medicine
Street address Sahlgrenska University Hospital
City Gothenburg
ZIP/Postal code 41345
Country Sweden
 
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (4)
GSM566102 MN1 leukemic_rep1
GSM566104 MN1 leukemic_rep2
GSM566153 Gr1/Mac1_rep1
Relations
BioProject PRJNA127611

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE22923_RAW.tar 15.6 Mb (http)(custom) TAR (of CEL, CHP)
Processed data included within Sample table
Processed data provided as supplementary file

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