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Series GSE32456 Query DataSets for GSE32456
Status Public on Aug 16, 2012
Title Co-addiction to IRF4 and SPIB in ABC-DLBCL
Organism Homo sapiens
Experiment type Expression profiling by array
Summary RNA interference screens identified the transcription factor IRF4 as essential for the survival of the activated B-cell-like subtype of diffuse large B-cell lymphoma (ABC-DLBCL). Analysis of IRF4 genomic targets in ABC-DLBCL and Multiple Myeloma (MM) revealed that IRF4 regulates distinct networks in these cancers. IRF4 peaks in ABC-DLBCL, but not MM, were enriched for a composite ETS-IRF DNA motif that can be bound by heterodimers of IRF4 and the ETS-family transcription factor SPIB, whose expression is also essential for ABC-DLBCL survival. Gene expression and ChIP-Seq analysis identified essential genes co-regulated by IRF4 and SPIB. Together, these factors regulate a critical oncogenic loop by activating CARD11, which controls ABC-DLBCL survival via the NF-kB pathway. The interaction between IRF4 and SPIB presents an attractive therapeutic target in this aggressive lymphoma.
 
Overall design Gene expression was analyzed using Agilent human 4X44K oligo gene expression arrays. Cell lines (HBL1, OCILY3, TMD8-ABC-DLBCL; KMS12-MM) were infected with control (shControl, Cy3), shIRF4_3'UTR (Cy5), shspiB_2_3'UTR (Cy5), shspib_2 (Cy5), chimeric repressor (Cy5) constructs, and changes in gene expression were monitored over time after induction of the shRNA with doxycyclin. For each of the three ABC-DLBCL cell line a four timepoint series (24, 48, 72, 96 hrs) of shRNA induction was analyzed, for a total of 12 arrays. In HBL-1 a second shRNA targeting the IRF4 cds (shIRF4_cds) was used in a similar time course of shRNA induction (4 arrays). Also in HBL-1 a shRNA targeting wild type SPIB (shspiB_2) was used in a similar time course of shRNA induction (4 arrays). Also in HBL-1 a shRNA targeting mutant SPIB (shspib_2) was used in a similar time course of shRNA induction (4 arrays). Also in HBL-1 an IRF4:SPIB chimeric repressor was used in a similar time course (4, 8, 24, 48 hrs) (4 arrays). For the KMS12 MM cell line a three point time course was analyzed using the shIRF4_3'UTR with one technical (using the same RNA sample) duplicate time point measurement (4 arrays).
 
Citation(s) 22698399
Submission date Sep 28, 2011
Last update date Feb 22, 2018
Contact name Louis M. Staudt
E-mail(s) lstaudt@mail.nih.gov
Phone 301-402-1892
Organization name National Cancer Institute
Department Lymphoid Malignancies Branch
Lab Louis M Staudt
Street address 9000 Rockville Pike, Bldg 10, Rm 4N114
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
 
Platforms (1)
GPL4133 Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Feature Number version)
Samples (32)
GSM565601 KMS12 shIRF4_3'UTR 48h - repeat 1 - mAdbID:87190
GSM565602 KMS12 shIRF4_3'UTR 96h - repeat 1 - mAdbID:87191
GSM565603 KMS12 shIRF4_3'UTR 96h - repeat 2 - mAdbID:87192
Relations
BioProject PRJNA147741

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
GSE32456_RAW.tar 463.2 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table
Processed data provided as supplementary file
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