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Figure 3

Figure 3. Reconstitution of A20-null cell lines causes apoptosis and cell growth arrest via inhibition of NF-kB. From: Mutations of multiple genes cause deregulation of NF-kB in diffuse large B-cell lymphoma.

a, Flow cytometric analysis of AnnexinV-PE/7AAD staining in A20-null and wild-type cell lines, transduced with the indicated vectors; numbers indicate the percentage of single and double-positive cells (lower and upper right quadrants). The results of 3 independent experiments are summarized in panel b (mean ± SD). c, Reduced viability in SUDHL2 cells complemented with A20 expression-vectors (red bars), as compared to vector alone (black bars)(mean±SD, n=3). No effect was observed in two control cell lines. d, Analysis of GFP expression after transduction with pWPI and pWPI-HA-A20 documents the disappearance of the GFP+ population in SUDHL2HA-A20 and RC-K8HA-A20, but not in SUDHL2pWPI and RC-K8pWPI or in A20 wild-type cell lines (mean ± SD, n=2). e) Immunofluorescence analysis of p105/p50 in SUDHL2 cells transduced with pWPI and pWPI-HA-A20 (top). Nuclei are identified by DAPI (bottom).

Mara Compagno, et al. Nature. ;459(7247):717-721.
Figure 2

Figure 2. Mutations and deletions of the A20 gene in ABC-DLBCL. From: Mutations of multiple genes cause deregulation of NF-kB in diffuse large B-cell lymphoma.

a) Percentage of A20 mutated cases in various DLBCL subtypes. The exact number over total analyzed is given on top. NC, samples co-expressing CD10 and IRF4 (see Methods). b) Schematic representation of the human A20 protein, with its key functional domains. Color-coded symbols depict distinct alterations leading to A20 inactivation. OTU, ovarian tumor domain; ZF, A-20 zinc-finger domains. c) Dual-color FISH analysis of representative DLBCLs, hybridized with A20-specific probes (red) and a chromosome 6 centromeric probe (green). Arrows point to representative cells displaying hemizygous (left panel) or homozygous (right panel) A20 deletions. d) Chromosome 6 ideogram; the region encompassing A20 on band 6q23 is enlarged in the bottom panel, where columns represent individual cases, and rows correspond to the two alleles. e) Overall frequency of A20 structural alterations (inactivating mutations and deletions, combined).

Mara Compagno, et al. Nature. ;459(7247):717-721.
Figure 1

Figure 1. The NF-kB pathway is active in ABC-DLBCL and in a smaller fraction of GCB-DLBCL. From: Mutations of multiple genes cause deregulation of NF-kB in diffuse large B-cell lymphoma.

a) Immunohistochemical staining of DLBCL biopsies with anti-NFKB1(p105/p50)(top) and anti-NFKB2(p100/p52)(bottom) antibodies. Nuclear localization of NF-kB denotes active signaling, as opposed to the inactive, cytoplasmic complex (200X). b) Prevalence of cases displaying constitutive NF-kB activation in DLBCL subgroups. Color codes indicate nuclear p50, p52 or both. c) Western blot analysis of DLBCL cell lines for processing of p100 to p52 (red, ABC-DLBCL; grey, GCB-DLBCL). The multiple myeloma cell line U266 and the epithelial cell line COS are used as positive and negative controls, respectively. Actin, loading control. d) GSEA enrichment score and distribution of NF-kB target genes along the rank of transcripts differentially expressed in ABC- vs GCB-DLBCL. e) Percentage of samples showing a transcriptional NF-kB signature by GSEA. f) Venn diagram illustrating the overlap between immunohistochemistry-defined and GSEA-defined NF-kB positive cases.

Mara Compagno, et al. Nature. ;459(7247):717-721.

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