title: Histone deacetylase inhibitor abexinostat affects chromatin organization and gene transcription in normal B cells and in mantle cell lymphoma.
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.
authors.affiliation: 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.
authors.forename: Diana
authors.initials: D
authors.lastname: Markozashvili
authors.affiliation: 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.
authors.forename: Andrei
authors.initials: A
authors.lastname: Pichugin
authors.affiliation: 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.
authors.forename: Ana
authors.initials: A
authors.lastname: Barat
authors.affiliation: Institut de Cancérologie Gustave-Roussy, F-94805 Villejuif, France.
authors.forename: Valerie
authors.initials: V
authors.lastname: Camara-Clayette
authors.affiliation: Kashkin Research Institute of Medical Mycology, Mechnikov North-Western State Medical University, Russia.
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Vasilyeva
authors.affiliation: Institut de Recherches International Servier, I.R.I.S., 50 rue Carnot, 92284 Suresnes Cedex, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Lelièvre
authors.affiliation: Institut de Recherches International Servier, I.R.I.S., 50 rue Carnot, 92284 Suresnes Cedex, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Kraus-Berthier
authors.affiliation: Institut de Recherches International Servier, I.R.I.S., 50 rue Carnot, 92284 Suresnes Cedex, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Depil
authors.affiliation: Institut de Cancérologie Gustave-Roussy, F-94805 Villejuif, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Ribrag
authors.affiliation: 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.
authors.forename: Yegor
authors.initials: Y
authors.lastname: Vassetzky
mesh_terms: D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001572:Benzofurans / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002843:Chromatin / Q000187:drug effects* / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D020522:Lymphoma, Mantle-Cell / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects*; D014178:Translocation, Genetic / Q000235:genetics
chemical_list: D001572:Benzofurans; D002843:Chromatin; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C512352:abexinostat
keywords: Cancer; Epigenetics; HDACi; Lymphoma; Transcription