NDLI: HDAC inhibitors and decitabine are highly synergistic and associated with unique gene-expression and epigenetic profiles in models of DLBCL

Content Provider	PubMed Central
Author	Kalac, Matko Scotto, Luigi Marchi, Enrica Amengual, Jennifer Seshan, Venkatraman E. Bhagat, Govind Ulahannan, Netha Leshchenko, Violetta V. Temkin, Alexis M. Parekh, Samir Benjamin, Tycko O'connor, Owen A.
Copyright Year	2011
Abstract	Interactions between histone deacetylase inhibitors (HDACIs) and decitabine were investigated in models of diffuse large B-cell lymphoma (DLBCL). A number of cell lines representing both germinal center B-like and activated B-cell like DLBCL, patient-derived tumor cells and a murine xenograft model were used to study the effects of HDACIs and decitabine in this system. All explored HDACIs in combination with decitabine produced a synergistic effect in growth inhibition and induction of apoptosis in DLBCL cells. This effect was time dependent, mediated via caspase-3 activation, and resulted in increased levels of acetylated histones. Synergy in inducing apoptosis was confirmed in patient-derived primary tumor cells treated with panobinostat and decitabine. Xenografting experiments confirmed the in vitro activity and tolerability of the combination. We analyzed the molecular basis for this synergistic effect by evaluating gene-expression and methylation patterns using microarrays, with validation by bisulfite sequencing. These analyses revealed differentially expressed genes and networks identified by each of the single treatment conditions and by the combination therapy to be unique with few overlapping genes. Among the genes uniquely altered by the combination of panobinostat and decitabine were VHL, TCEB1, WT1, and DIRAS3.
Related Links	http://dx.doi.org/10.1182/blood-2011-02-336891
Ending Page	5516
Page Count	11
Starting Page	5506
File Format	PDF
ISSN	00064971
e-ISSN	15280020
Journal	Blood
Issue Number	20
Volume Number	118
Language	English
Publisher	American Society of Hematology
Publisher Date	2011-11-17
Access Restriction	Open
Rights Holder	American Society of Hematology
Subject Keyword	Immunology Cell Biology Biochemistry Hematology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Hematology Biochemistry Immunology

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