DNMTi/HDACi combined epigenetic targeted treatment induces reprogramming of myeloma cells in the direction of normal plasma cells

• Verfasst von: Bruyer, Angelique [VerfasserIn]
• Verfasst von: Seckinger, Anja [VerfasserIn]
• Verfasst von: Müller-Tidow, Carsten [VerfasserIn]
• Verfasst von: Goldschmidt, Hartmut [VerfasserIn]
• Verfasst von: Hose, Dirk [VerfasserIn]
• Titel: DNMTi/HDACi combined epigenetic targeted treatment induces reprogramming of myeloma cells in the direction of normal plasma cells
• Verf.angabe: Angelique Bruyer, Ken Maes, Laurie Herviou, Alboukadel Kassambara, Anja Seckinger, Guillaume Cartron, Thierry Rème, Nicolas Robert, Guilhem Requirand, Stéphanie Boireau, Carsten Müller-Tidow, Jean-luc Veyrune, Laure Vincent, Salahedine Bouhya, Hartmut Goldschmidt, Karin Vanderkerken, Dirk Hose, Bernard Klein, Elke De Bruyne and Jerome Moreaux
• E-Jahr: 2018
• Jahr: 2 March 2018
• Umfang: 12 S.
• Fussnoten: Gesehen am 17.10.2019
• Titel Quelle: Enthalten in: British journal of cancer
• Ort Quelle: Edinburgh : Nature Publ. Group, 1999
• Jahr Quelle: 2018
• Band/Heft Quelle: 118(2018), 8, Seite 1062-1073
• ISSN Quelle: 1532-1827
• DOI: doi:10.1038/s41416-018-0025-x
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1679048783

Abstract

Multiple myeloma (MM) is the second most common hematologic malignancy. Aberrant epigenetic modifications have been reported in MM and could be promising therapeutic targets. As response rates are overall limited but deep responses occur, it is important to identify those patients who could indeed benefit from epigenetic-targeted therapy. Since HDACi and DNMTi combination have potential therapeutic value in MM, we aimed to build a GEP-based score that could be useful to design future epigenetic-targeted combination trials. In addition, we investigated the changes in GEP upon HDACi/DNMTi treatment. We report a new gene expression-based score to predict MM cell sensitivity to the combination of DNMTi/HDACi. A high Combo score in MM patients identified a group with a worse overall survival but a higher sensitivity of their MM cells to DNMTi/HDACi therapy compared to a low Combo score. In addition, treatment with DNMTi/HDACi downregulated IRF4 and MYC expression and appeared to induce a mature BMPC plasma cell gene expression profile in myeloma cell lines. In conclusion, we developed a score for the prediction of primary MM cell sensitivity to DNMTi/HDACi and found that this combination could be beneficial in high-risk patients by targeting proliferation and inducing maturation.