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Series GSE25643 Query DataSets for GSE25643
Status Public on Nov 30, 2016
Title Antagonism of B cell enhancer networks by STAT5 drives leukemia and poor patient survival
Organism Mus musculus
Experiment type Expression profiling by array
Summary The transcription factor STAT5 plays a critical role in B cell acute lymphoblastic leukemia (B-ALL). How STAT5 mediates this effect is unclear. Here we demonstrate that STAT5 activation cooperates with defects in the pre-BCR signaling components encoded by Blnk, Btk, Prkcb, Nfkb1, and Ikzf1 to initiate B-ALL. STAT5 antagonizes NF-κB and IKAROS by opposing regulation of shared target genes. STAT5 binding was enriched at super-enhancers, which were associated with an opposing network of transcription factors, including PAX5, EBF1, PU.1, IRF4, and IKAROS. Patients with high ratios of active STAT5 to NF-κB or IKAROS have more aggressive disease. Our studies illustrate that an imbalance of two opposing transcriptional programs drive B-ALL, and suggest that restoring the balance of these pathways may inhibit B-ALL.
Overall design Gene expression profiling was performed on cells isolated from lymph nodes of Stat5b-CA, Stat5b-CA x Blnk+/-, Stat5b-CA x Xid-/-, Stat5b-CA x Pkrcb-/-, Stat5b-CA x Ebf1+/- and Stat5b-CA x Rag2-/- leukemic mice and pre B cells sorted from bone marrow of C57BL/6 wild type mice, Xid Mice, and Stat5b-CA non-leukemic mice. 40 Samples.
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Contributor(s) Katerndahl C, Heltemes-Harris LM, Willette M, Henzler CM, Fritze S, Yang R, Schjerven H, Silverstein K, Ramsey LB, Hubbard G, Wells A, Kuiper RP, Scheijen B, van Leeuwen FN, Müschen M, Kornblau SM, Farrar MA
Citation(s) 28369050
Submission date Nov 29, 2010
Last update date Feb 11, 2019
Contact name Lynn Heltemes Harris
Organization name University of Minnesota
Street address 2101 6th St. SE
City Minneapolis
State/province MN
ZIP/Postal code 55455
Country USA
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (40)
GSM630049 WT preB #1
GSM630050 WT preB #2
GSM630051 WT preB #3
BioProject PRJNA133897

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Supplementary file Size Download File type/resource
GSE25643_RAW.tar 166.3 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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