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Series GSE68505 Query DataSets for GSE68505
Status Public on Dec 09, 2015
Title ATM-deficient B cell lymphomas
Organism Mus musculus
Experiment type Expression profiling by array
Summary Ataxia-telangiectasia mutated (ATM) kinase plays a central role in maintaining genomic integrity. In both humans and mice, ATM deficiency is associated with an increased incidence of lymphoid cancers that are primarily T cell in origin. We demonstrate here that when T cells are removed as targets for lymphomagenesis and as mediators of immune surveillance, ATM-deficient mice exclusively develop early onset IgM+ B cell lymphomas that by histology and gene expression profiling resemble the activated B cell-like (ABC) subset of human diffuse large B cell lymphomas (DLBCL). These ATM-deficient B cell tumors show considerable chromosomal instability and a recurrent genomic amplification of a 4.48 Mb region on chromosome 18 that contains Malt1 and is orthologous to a region similarly amplified in human ABC-DLBCL. Further, the amplification of Malt1 in these lymphomas correlates with their dependence on NF-kB, MALT1, and BCR signaling for survival, paralleling human ABC-DLBCL. This study reveals that ATM protects against development of B cell lymphomas that model human ABC-DLBCL and identifies a role for T cells in preventing the emergence of these tumors.
Overall design We performed gene expression profiling on nine ATMKO.CD3epsilonKO lymphoma cell lines (n=12, 3 technical repeats). We analyzed gene expression of anti-IgM stimulated primary B cells from both ATMKO.CD3epsilonKO (n=7, 5 technical repeats) and ATMWT.CD3epsilonKO mice (n=2), and GC B cells isolated from SRBC-immunized ATMWT mice (n=3, 1 biological repeat and 2 technical repeats). We analyzed gene expression following treatment of two ATMKO.CD3epsilonKO lymphoma cell lines with the BTK inhibitor, PCI-32765, at time points (1, 3, 6, and 24 hours) as compared to time points with vehicle (DMSO) (n=8).
Citation(s) 26400962
Submission date May 04, 2015
Last update date Jul 19, 2017
Contact name Louis M. Staudt
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)
GPL13912 Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Feature Number version)
Samples (32)
GSM1673918 B cell lymphoma 178119 - PCI-32765 treated 1 hr - mAdbID:127901
GSM1673919 B cell lymphoma 178119 - PCI-32765 treated 3 hr - mAdbID:127902
GSM1673920 B cell lymphoma 178119 - PCI-32765 treated 6 hr - mAdbID:127903
BioProject PRJNA282948

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Supplementary file Size Download File type/resource
GSE68505_RAW.tar 667.8 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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