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| Status |
Public on Feb 08, 2017 |
| Title |
Critical role of PI3K signaling for NF-κB–dependent survival in a subset of activated B-cell–like diffuse large B-cell lymphoma cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
The activated B-cell–like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) represents a very aggressive human lymphoma entity. Constitutive NF-κB activation caused by chronic active B-cell receptor (BCR) signaling is common feature of many ABC DLBCL cells; however, the pathways linking BCR signaling to the NF-κB prosurvival network are largely unknown. Here we report that constitutive activity of PI3K and the downstream kinase PDK1 are essential for the viability of two ABC DLBCL cell lines that carry mutations in the BCR proximal signaling adaptor CD79B. In these cells, PI3K inhibition reduces NF-κB activity and decreases the expression of NF-κB target genes. Furthermore, PI3K and PDK1 are required for maintaining MALT1 protease activity, which promotes survival of the affected ABC DLBCL cells. These results demonstrate a critical function of PI3K-PDK1 signaling upstream of MALT1 pro- tease and NF-κB in distinct ABC DLBCL cells and provide a rationale for the pharmacologic use of PI3K inhibitors in DLBCL therapy.
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| Overall design |
This GEO dataset is comprised of three experiments: a) 4 paired (2-color) GEP measurements following treatment with the PI3K inhibitor 15e in the DLBCL cell line HBL1. b) 4 paired (2-color) GEP measurements following treatment with the same PI3K inhibitor 15e in the DLBCL cell line TMD8. c) 4 paired (2-color) GEP measurements following treatment with the IKKbeta inhibitor MLN120b in the DLBCL cell line HBL1.
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| Contributor(s) |
Lenz G |
| Citation(s) |
21173233 |
| |
| Submission date |
Feb 07, 2017 |
| Last update date |
Feb 22, 2018 |
| Contact name |
Michael Grau |
| Organization name |
University of Münster
|
| Department |
Faculty of Medicine
|
| Lab |
Translational Oncology
|
| Street address |
Albert-Schweitzer-Campus 1
|
| City |
Münster |
| State/province |
Nordrhein-Westfalen |
| ZIP/Postal code |
48149 |
| Country |
Germany |
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| Platforms (1) |
| GPL4133 |
Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Feature Number version) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA371600 |
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