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Series GSE27226 Query DataSets for GSE27226
Status Public on Feb 15, 2011
Title HDACI and DAC induce specific epigenetic profile in DLBCL
Organism Homo sapiens
Experiment type Expression profiling by array
Methylation profiling by array
Summary Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoid neoplasm in the world representing 30-40% of all lymphomas. Standard immunochemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab) ensures cure in 60 to 65% of patients, while the rest progress or relapse. While advances have been made in the treatment of DLBCL, especially with the addition of rituximab, it is now apparent that there may be significant differences in prognosis that are related to the cell of origin, and that this disease is heterogeneous and novel treatment options are needed. It has been hypothesized that the combination of HDACI and hypomethylating agents might be a new approach to the treatment of relapsed or refractory DLBCL. This combination is thought to disrupt the transcription repressor complex consisting of methyl binding domain proteins (MBDP) and histone deacetylases (HDACs). We have explored the effect of different HDACI and decitabine combinations in in vitro and in vivo models of DLBCL. These data suggest a class effect, with all four HDACI (panobinostat, belinostat, vorinostat, depsipeptide) synergizing with decitabine in cytotoxicity assay across the spectrum of DLBCL cells. Synergy was validated in a number of other assays including a caspase 3 activation and apoptosis. Furthermore, the combination of panobinostat and decitabine induced markedly increased histone acetylation. The in vitro observations were confirmed in an in vivo murine xenograft experiment with the Ly1 DLBCL line. Genome wide methylation analysis and gene expression profiling demonstrated that the combination of these two epigenetic therapies produced a unique gene expression profile compared to the samples treated with single drugs. These data strongly support the potential therapeutic role of a combinatorial epigenetic platform for the treatment of B-cell lymphomas, in particular in patients with DLBCL. Clearly, future studies will need to focus on integrating the appropriate correlative studies, with an effort to identify and or validate biomarkers of activity with these combinations. The likelihood moving forward is that the mechanism of action of these combinations may vary from disease context to disease context. Genome-wide array findings from these kinds of studies could be expanded to samples from patients on clinical trials to identify novel biomarkers of response, leading to the rational treatment of individual diseases based upon the underlying pathogenesis.
 
Overall design We have used single samples from three DLBCL cell lines (biological replicates) which were treated with DMSO, decitabine alone, panobinostat alone and their combination for 48h - total of 12 samples
 
Contributor(s) Kalac M, Scotto L, Marchi E, Amengual J, Seshan VE, Bhagat G, Ulahannan N, Leshchenko VV, Parekh S, Tycko B, O'Connor OA
Citation(s) 21772049
Submission date Feb 10, 2011
Last update date Aug 16, 2018
Contact name Matko Kalac
E-mail(s) matko.kalac@nyumc.org
Phone 212 263 9124
Organization name NYU Medical Center
Department NYU Cancer Institute
Lab O'Connor-Smilow 1207
Street address 522 1st Avenue
City New York
State/province NY
ZIP/Postal code 10016
Country USA
 
Platforms (2)
GPL6947 Illumina HumanHT-12 V3.0 expression beadchip
GPL8490 Illumina HumanMethylation27 BeadChip (HumanMethylation27_270596_v.1.2)
Samples (24)
GSM673047 OCI-Ly1 control 48h
GSM673048 OCI-Ly1 decitabine 48h
GSM673049 OCI-Ly1 panobinostat 48h
Relations
BioProject PRJNA137503

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE27226_GSM673047-GSM673058-non-normalized.txt.gz 4.4 Mb (ftp)(http) TXT
GSE27226_GSM673107-GSM673118-non-normalized.txt.gz 11.9 Mb (ftp)(http) TXT
GSE27226_RAW.tar 12.0 Mb (http)(custom) TAR
Processed data included within Sample table

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