Bruno, Tiziana, De Nicola, Francesca, Corleone, Giacomo ORCID: 0000-0002-6170-9780, Catena, Valeria ORCID: 0000-0002-9639-1944, Goeman, Frauke, Pallocca, Matteo ORCID: 0000-0002-7756-3579, Sorino, Cristina ORCID: 0000-0002-6100-289X, Bossi, Gianluca ORCID: 0000-0002-2947-1063, Amadio, Bruno, Cigliana, Giovanni, Ricciardi, Maria Rosaria, Petrucci, Maria Teresa, Spugnini, Enrico Pierluigi, Baldi, Alfonso ORCID: 0000-0002-8693-3842, Cioce, Mario, Cortese, Giancarlo, Mattei, Elisabetta, Merola, Roberta, Gianelli, Umberto, Baldini, Luca, Pisani, Francesco, Gumenyuk, Svitlana, Mengarelli, Andrea ORCID: 0000-0002-2606-2467, Hopker, Katja, Benzing, Thomas, Vincenzi, Bruno, Floridi, Aristide, Passananti, Claudio, Blandino, Giovanni, Iezzi, Simona ORCID: 0000-0002-7484-5861 and Fanciulli, Maurizio (2020). Che-1/AATF-induced transcriptionally active chromatin promotes cell proliferation in multiple myeloma. Blood Adv., 4 (22). S. 5616 - 5631. WASHINGTON: AMER SOC HEMATOLOGY. ISSN 2473-9537

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Abstract

Multiplemyeloma (MM) is a hematologicmalignancy produced by a clonal expansion of plasma cells and characterized by abnormal production and secretion of monoclonal antibodies. This pathologyexhibitsanenormousheterogeneity resultingnot onlyfromgenetic alterations but also from several epigenetic dysregulations. Here we provide evidence that Che-1/AATF (Che-1), an interactor of RNA polymerase II, promotes MM proliferation by affecting chromatin structure and sustaining global gene expression. We found that Che-1 depletion leads to a reduction of active chromatin by inducing a global decrease of histone acetylation. In this context, Che-1 directly interacts with histones and displaces histone deacetylase class I members from them. Strikingly, transgenic mice expressing human Che-1 in plasma cells develop MM with clinical features resembling those observed in the human disease. Finally, Che-1 downregulation decreases BRD4 chromatin accumulation to further sensitize MM cells to bromodomain and external domain inhibitors. These findings identify Che-1 as a promising target forMMtherapy, alone or in combination with bromodomain and external domain inhibitors.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Bruno, TizianaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
De Nicola, FrancescaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Corleone, GiacomoUNSPECIFIEDorcid.org/0000-0002-6170-9780UNSPECIFIED
Catena, ValeriaUNSPECIFIEDorcid.org/0000-0002-9639-1944UNSPECIFIED
Goeman, FraukeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pallocca, MatteoUNSPECIFIEDorcid.org/0000-0002-7756-3579UNSPECIFIED
Sorino, CristinaUNSPECIFIEDorcid.org/0000-0002-6100-289XUNSPECIFIED
Bossi, GianlucaUNSPECIFIEDorcid.org/0000-0002-2947-1063UNSPECIFIED
Amadio, BrunoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cigliana, GiovanniUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ricciardi, Maria RosariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Petrucci, Maria TeresaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spugnini, Enrico PierluigiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baldi, AlfonsoUNSPECIFIEDorcid.org/0000-0002-8693-3842UNSPECIFIED
Cioce, MarioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cortese, GiancarloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mattei, ElisabettaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Merola, RobertaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gianelli, UmbertoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baldini, LucaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pisani, FrancescoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gumenyuk, SvitlanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mengarelli, AndreaUNSPECIFIEDorcid.org/0000-0002-2606-2467UNSPECIFIED
Hopker, KatjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Benzing, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vincenzi, BrunoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Floridi, AristideUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Passananti, ClaudioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blandino, GiovanniUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Iezzi, SimonaUNSPECIFIEDorcid.org/0000-0002-7484-5861UNSPECIFIED
Fanciulli, MaurizioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-310809
DOI: 10.1182/bloodadvances.2020002566
Journal or Publication Title: Blood Adv.
Volume: 4
Number: 22
Page Range: S. 5616 - 5631
Date: 2020
Publisher: AMER SOC HEMATOLOGY
Place of Publication: WASHINGTON
ISSN: 2473-9537
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
SELECTIVE-INHIBITION; C-MYC; EXPRESSION; MECHANISMS; REPRESSION; ADDICTION; HDAC1; IRF4Multiple languages
HematologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/31080

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