Transcriptomics

Dataset Information

0

HDACI and DAC induce specific epigenetic profile in DLBCL


ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE27226 | GEO | 2011/02/15

SECONDARY ACCESSION(S): PRJNA137503

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2011-02-15 | E-GEOD-27226 | biostudies-arrayexpress
2014-04-09 | E-GEOD-56623 | biostudies-arrayexpress
2016-12-31 | GSE73966 | GEO
2016-12-31 | GSE74036 | GEO
2017-02-08 | GSE78102 | GEO
2016-08-01 | E-GEOD-59308 | biostudies-arrayexpress
2014-09-01 | E-GEOD-54201 | biostudies-arrayexpress
2014-09-01 | GSE54201 | GEO
2014-04-09 | GSE56623 | GEO
2023-10-22 | GSE211829 | GEO