Histone deacetylase inhibitor abexinostat affects chromatin organization and gene transcription in normal B cells and in mantle cell lymphoma

Diana Markozashvili; Andrei Pichugin; Ana Barat; Valerie Camara-Clayette; Natalia V Vasilyeva; Hélène Lelièvre; Laurence Kraus-Berthier; Stéphane Depil; Vincent Ribrag; Yegor Vassetzky

doi:10.1016/j.gene.2016.01.017

Histone deacetylase inhibitor abexinostat affects chromatin organization and gene transcription in normal B cells and in mantle cell lymphoma

Gene. 2016 Apr 15;580(2):134-143. doi: 10.1016/j.gene.2016.01.017. Epub 2016 Jan 13.

Affiliations

¹ UMR 8126, Univ. Paris-Sud, CNRS, Institut de Cancérologie Gustave-Roussy, F-94805 Villejuif, France; LIA 1066 Laboratoire franco-russe de recherche en oncologie, F-94805 Villejuif, France.
² UMR 8126, Univ. Paris-Sud, CNRS, Institut de Cancérologie Gustave-Roussy, F-94805 Villejuif, France; LIA 1066 Laboratoire franco-russe de recherche en oncologie, F-94805 Villejuif, France; Peter the Great St. Petersburg Polytechnic University, St-Petersburg, Russia.
³ Institut de Cancérologie Gustave-Roussy, F-94805 Villejuif, France.
⁴ Kashkin Research Institute of Medical Mycology, Mechnikov North-Western State Medical University, Russia.
⁵ Institut de Recherches International Servier, I.R.I.S., 50 rue Carnot, 92284 Suresnes Cedex, France.
⁶ UMR 8126, Univ. Paris-Sud, CNRS, Institut de Cancérologie Gustave-Roussy, F-94805 Villejuif, France; LIA 1066 Laboratoire franco-russe de recherche en oncologie, F-94805 Villejuif, France; Koltzov Institute of Developmental Biology, Moscow, Russia. Electronic address: vassetzky@igr.fr.

PMID: 26774800
DOI: 10.1016/j.gene.2016.01.017

Abstract

Mantle cell lymphoma (MCL) is a rare lymphoma caused by the t(11:14) juxtaposing the cyclin D1 (CCND1) locus on chromosome 11 and the immunoglobulin heavy chain (IgH) locus on chromosome 14. Several new treatments are proposed for MCL, including histone deacetylase inhibitors (HDACi). We have studied gene expression and chromatin organization in the translocated 11q13 locus in MCL cells as compared to lymphoblastoid cell lines as well as the effect of HDACi abexinostat on chromatin organization and gene expression in the 11q13 locus. We have identified a cluster of genes overexpressed in the translocation region on chromosome 11 in MCL cells. Abexinostat provokes a genome-wide disaggregation of heterochromatin. The genes upregulated after the t(11;14) translocation react to the HDACi treatment by increasing their expression, but their gene promoters do not show significant alterations in H3K9Ac and H3K9me2 levels in abexinostat-treated cells.

Keywords: Cancer; Epigenetics; HDACi; Lymphoma; Transcription.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

B-Lymphocytes / drug effects*
B-Lymphocytes / metabolism
B-Lymphocytes / pathology
Benzofurans / pharmacology*
Cell Line, Tumor
Chromatin / drug effects*
Chromatin / metabolism
Chromatin Assembly and Disassembly / drug effects
Chromosomes, Human, Pair 11 / genetics
Chromosomes, Human, Pair 14 / genetics
Gene Expression Regulation, Neoplastic / drug effects
Histone Deacetylase Inhibitors / pharmacology*
Humans
Hydroxamic Acids / pharmacology*
Lymphoma, Mantle-Cell / genetics*
Lymphoma, Mantle-Cell / pathology
Promoter Regions, Genetic / drug effects
Transcription, Genetic / drug effects*
Translocation, Genetic / genetics

Substances

Benzofurans
Chromatin
Histone Deacetylase Inhibitors
Hydroxamic Acids
abexinostat