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Title: NF-kB2 mutation targets survival, proliferation and differentiation pathways in the pathogenesis of B-lineage lymphomas      
keywords:
Transcriptome or Gene expression
ID:
PRJNA143995
description:
Abnormal NF-kB2 activation has been reported in several types of human leukemia and lymphomas although the exact mechanisms and affected pathways are not clear. We have investigated these questions through the use of a unique transgenic mouse model with lymphocyte-targeted expression of p80HT, a lymphoma associated NF-kB2 mutant. Microarray analysis, verified at the RNA and protein level identified new downstream targets and confirmed established regulatory networks. 201 genes were significantly changed, with 126 being upregulated and 75 downregulated. Pathway analysis uncovered both known and unknown interactions between factors important in the development of human B cell lymphomas and multiple myeloma, including cyclins D1 and D2, TRAF1, CD27, BIRC5/survivin, IL-15 and IL-10. Critical roles for STAT3 and TNF receptors are highlighted. Six target genes of STAT3 were identified: cyclins D1and D2, IL-10, survivin, IL-21 and Blimp1. Interfering with STAT3 signaling induced apoptosis in multiple myeloma cell lines. Novel pathways for NF-kB2 are proposed that involve IL-10 and other genes in the differentiation of plasma cells, evasion of apoptosis and proliferation. These pathways were verified with publically available human microarrays. Several treatment strategies based on these findings are discussed. Overall design: RNA was isolated from the B cells of p80HT transgenic mice on the C57BL/6J x SJL/J background , which produced serum monoclonal immunoglobulin (M-protein) (n=3), and the B cells from wild type (WT) littermates (n=3) using Trizol reagent according to the manufacturer’s instructions (Invitrogen, Carlsbad, CA). RNA was further prepared with the Ambion WT Expression kit (Life Techologies Corp., Carlsbad, CA) then run on the Mouse Gene 1.0ST microarray chip (Affymetrix, Santa Clara, CA).
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA143995
authentication:
none
authorization:
none
ID:
pmid:22642622
name:
Mus musculus
ncbiID:
ncbitax:10090
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject