Standard name LU_IL4_SIGNALING
Systematic name M10558
Brief description Genes up-regulated in peripheral B lymphocytes after incubation with IL4 [GeneID=3565] for 4 h.
Full description or abstract Diffuse large B-cell lymphomas (DLBCLs) can be subclassified into germinal center B-cell (GCB)-like and activated B-cell (ABC)-like tumors characterized by long and short survival, respectively. In contrast to ABC-like DLBCL, GCB-like tumors exhibit high expression of components of the interleukin 4 (IL-4) signaling pathway and of IL-4 target genes such as BCL6 and HGAL, whose high expression independently predicts better survival. These observations suggest distinct activity of the IL-4 signaling pathway in DLBCL subtypes. Herein, we demonstrate similar IL-4 expression but qualitatively different IL-4 effects on GCB-like and ABC-like DLBCL. In GCB-like DLBCL, IL-4 induces expression of its target genes, activates signal transducers and activators of transcription 6 (STAT6) signaling, and increases cell proliferation. In contrast, in the ABC-like DLBCL, IL-4 activates AKT, decreases cell proliferation by cell cycle arrest, and does not induce gene expression due to aberrant Janus kinase (JAK)-STAT6 signaling attributed to STAT6 dephosphorylation. We found distinct expression profiles of tyrosine phosphatases in DLBCL subtypes and identified putative STAT6 tyrosine phosphatases-protein tyrosine phosphatase nonreceptor type 1 (PTPN1) and PTPN2, whose expression is significantly higher in ABC-like DLBCL. These differences in tyrosine phosphatase expression might underlie distinct expression profiles of some of the IL-4 target genes and could contribute to a different clinical outcome of patients with GCB-like and ABC-like DLBCLs.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 15591113   Authors: Lu X,Nechushtan H,Ding F,Rosado MF,Singal R,Alizadeh AA,Lossos IS
Exact source Table 1S
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Organism Homo sapiens
Contributed by Kate Stafford (MSigDB Team)
Source platform HUMAN_GENE_SYMBOL
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Version history 3.0: Renamed from LU_IL4BCELL

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