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Series GSE34224 Query DataSets for GSE34224
Status Public on Dec 31, 2012
Title Interaction of c-Myb with p300 is required for the induction of acute myeloid leukemia (AML) by human AML oncogenes
Organism Mus musculus
Experiment type Expression profiling by array
Summary The MYB oncogene is widely expressed in acute leukemias and is important for the continued proliferation of leukemia cells, raising the possibility that MYB may be a therapeutic target. However realization of this potential requires (i) a significant therapeutic window for MYB inhibition, given its essential role in normal hematopoiesis; and (ii) an approach for developing an effective therapeutic. We previously showed that the interaction of Myb with the coactivator CBP/p300 is essential for its transforming activity. Here we use hematopoietic cells from the Booreana mouse strain, which carries a mutation in Myb that prevents interaction with CBP/p300, to examine the requirement for this interaction in myeloid transformation and leukemogenesis. Using this strain and a strain (plt6) carrying a “complementary” mutation in p300, we show that the Myb-p300 interaction is essential for in vitro transformation by the myeloid leukemia oncogenes AML1-ETO, AML1-ETO9a, MLL-ENL, and MLL-AF9. We further show that unlike cells from wild-type (WT) mice, Booreana cells fail to induce leukemia upon transplantation into irradiated recipients following transduction with an AML1-ETO9a retrovirus. These data highlight disruption of the Myb-p300 interaction as a potential therapeutic strategy for AML and suggest that such a strategy would have a useable therapeutic index since Booreana mice, unlike Myb null mice, are viable. Finally we have begun to explore the molecular basis of the these observations by gene expression profiling; this highlighted several genes previously implicated in myeloid leukemogenesis as being differentially expressed between WT and Booreana cells transduced with AML1-ETO9a.
 
Overall design Total RNA was obtained from FACS sorted GFP+;c-Kit+ primary bone marrow cells from WT and Booreana mouse strains which had been cultured for 48 hours post-transduction with Control or AML1-ETO9a retroviruses. RNA was extracted from each of 4 samples per group and used to probe Illumina mouse Beadchips array.
 
Contributor(s) Shakhbazov K, Patabiraman DR, Gonda TJ
Citation(s) 24596419
Submission date Dec 07, 2011
Last update date Jun 14, 2018
Contact name Konstantin Shakhbazov
Organization name UQDI
Street address Ipswich Road
City Brisbane
ZIP/Postal code 4102
Country Australia
 
Platforms (1)
GPL6885 Illumina MouseRef-8 v2.0 expression beadchip
Samples (16)
GSM844850 Boo AML1-ETO9a replicate 1
GSM844851 Boo AML1-ETO9a replicate 2
GSM844852 Boo AML1-ETO9a replicate 3
Relations
BioProject PRJNA149777

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
GSE34224_RAW.tar 3.1 Mb (http)(custom) TAR
GSE34224_non-normalized_data.txt.gz 2.5 Mb (ftp)(http) TXT
Raw data are available on Series record
Processed data included within Sample table

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