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| Status |
Public on Aug 01, 2016 |
| Title |
Differentiation of DLBCL induced by HDAC inhibitors is associated with sensitization to proteasome inhibition |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Epigenetic modifying enzymes are commonly mutated in diffuse large B cell lymphoma (DLBCL), suggesting that epigenetic regulation is an important factor in DLBCL pathogenesis and a potential target for therapy. We developed resistant cell lines to histone deacetylase inhibitors (HDACi), one such epigenetic therapy, in order to define mechanisms of response and resistance. Strikingly, using gene expression and metabolic profiling, we found that development of HDACi resistance was associated with differentiation toward a plasmablast-like phenotype. Differentiation correlated with decreased B cell receptor signaling, increased ER stress and activation of the unfolded protein response, and increased sensitivity to proteasome inhibitors. Importantly, we found evidence of differentiation in lymphoma biopsies from patients treated with HDACi. Together, these data show, for the first time, that HDACi are differentiating agents in lymphoma and may be used to prime DLBCL for targeted therapy including proteasome inhibitors.
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| Overall design |
Gene expression in DLBCL cells from tumor biopsies after 15 days panobinostat therapy
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| Contributor(s) |
Mann KK, Miller WH |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Jul 10, 2014 |
| Last update date |
Jan 09, 2018 |
| Contact name |
Koren Mann |
| Organization name |
Lady Davis Institute
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| Lab |
Dr. Koren Mann
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| Street address |
3755 Cote Ste Catherine
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| City |
Montreal |
| State/province |
Quebec |
| ZIP/Postal code |
H3T1E2 |
| Country |
Canada |
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| Platforms (2) |
| GPL14550 |
Agilent-028004 SurePrint G3 Human GE 8x60K Microarray (Probe Name Version) |
| GPL17077 |
Agilent-039494 SurePrint G3 Human GE v2 8x60K Microarray 039381 (Probe Name version) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA255039 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE59308_RAW.tar |
18.2 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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