Comment[ArrayExpressAccession]	E-GEOD-46873
MAGE-TAB Version	1.1						
Public Release Date	2013-06-01
Investigation Title	Dual targeting of MYC and CYCLON by BET bromodomain inhibition optimizes Rituximab response in lymphoma.						
Comment[Submitted Name]	Dual targeting of MYC and CYCLON by BET bromodomain inhibition optimizes Rituximab response in lymphoma.
Experiment Description	Immuno-chemotherapy regimens elicit high response rates in B-cell non-Hodgkin lymphoma but heterogeneity in response duration is observed, with some patients achieving cure and others showing refractory disease or relapse. Using a transcriptome-powered targeted proteomics screen, we discovered a gene regulatory circuit involving the nuclear factor CYCLON which characterizes aggressive disease and resistance to the anti-CD20 monoclonal antibody, Rituximab, in high-risk B-cell lymphoma. CYCLON knockdown was found to inhibit the aggressivity of MYC-overexpressing tumors in mice and to modulate gene expression programs of biological relevance to lymphoma. Furthermore, CYCLON knockdown increased the sensitivity of human lymphoma B cells to Rituximab in vitro and in vivo. Strikingly, this effect could be mimicked by in vitro treatment of lymphoma B cells with a small molecule inhibitor for BET bromodomain proteins (JQ1). In summary, this work has identified CYCLON as a new MYC cooperating factor that drives aggressive tumor growth and Rituximab resistance in lymphoma. This resistance mechanism is amenable to next-generation epigenetic therapy by BET bromodomain inhibition, thereby providing a new combination therapy rationale for high-risk lymphoma. We have identified CYCLON has a nuclear factor involved in tumor progression and treatment resistance in aggressive lymphoma. In order to get further insights into the molecular mechanisms related to the expression of this factor, we used Raji cells to compared  gene expression profiles of control and CYCLON knock-down cell lines. Stable cell lines have been established using lentiviral transduction of Raji Burkitt lymphoma B cells with either a control (non-targeting) shRNA sequence or CYCLON shRNA constructs under puromycin selection. Non-transduced cells were also analyzed as a control. 4 replicates were analyzed for each conditions.						
Term Source Name	ArrayExpress	EFO
Term Source File	http://www.ebi.ac.uk/arrayexpress/	http://www.ebi.ac.uk/efo/efo.owl					
Person Last Name	Emadali	Emadali	Rousseaux	Khochbin	Callanan		
Person First Name	Anouk	Anouk	Sophie	Saadi	Mary		
Person Email	anouk.emadali@ujf-grenoble.fr						
Person Affiliation	Institut Albert Bonniot						
Person Address	Institut Albert Bonniot, BP170, Grenoble, France						
Person Roles	submitter						
Protocol Name	P-GSE46873-1	P-GSE46873-5	P-GSE46873-6	P-GSE46873-2	P-GSE46873-3	P-GSE46873-4	P-GSE46873-7
Protocol Description	The data were analyzed with GeneSpring software (v.11.0, Agilent) using default analysis settings and RMA normalization (with no baseline transormation). ID_REF =  VALUE = Log2 RMA-normalized signal intensity	Biotinylated cRNA was prepared using the kit GeneChip IVT express according to manufacturer’s instructions.	cRNA was hybridized to HG U133 Plus 2.0 microarrays according to manufacturer’s instructions.	Stable cell lines have been established using lentiviral transduction of Raji cells with either a control (non-targeting) shRNA sequence or CYCLON shRNA constructs under puromycin selection.	Raji cells were cultured in RPMI supplemented with 20 % fœtal bovine serum, sodium pyruvate, non esssential amino acids and penicilllin/streptomycin.	Trizol extraction of total RNA was performed according to the manufacturer's instructions.	Fluorescence intensities were quantified using the GCOS 1.2 software
Protocol Type	normalization data transformation protocol	labelling protocol	hybridization protocol	sample treatment protocol	growth protocol	nucleic acid extraction protocol	array scanning protocol
Experimental Factor Name	TRANSDUCED WITH						
Experimental Factor Type	transduced with						
Comment[SecondaryAccession]	GSE46873						
Comment[GEOReleaseDate]	2013-06-01						
Comment[ArrayExpressSubmissionDate]	2013-05-13						
Comment[GEOLastUpdateDate]	2013-06-07						
Comment[AEExperimentType]	transcription profiling by array						
SDRF File	E-GEOD-46873.sdrf.txt