Combination of decitabine and JNJ-26481585 triggers synergistic anti-myeloma activity

Ken Maes, Miguel Lemaire, J. Arts, Els Van Valckenborgh, Eline Menu, Hendrik De Raeve, Helena Jernberg-Wiklund, Ivan Van Riet, Karin Vanderkerken, Elke De Bruyne

Onderzoeksoutput: Conference paper

Samenvatting

DNA methylation and histone acetylation are currently the best understood epigenetic modifications. In multiple myeloma (MM), the epigenetic landscape is often disturbed as evidenced by changes in the
above modifications. Interfering with them using a DNA methylation inhibitor (DNMTi) or a histone deacetylation inhibitor (HDACi) has anti-myeloma effects. We hypothesized that combining both drugs
enhances their anti-MM effects. Here, we investigated the potential of combining the DNMTi decitabine (DAC) and the HDACi JNJ-26481585 (JNJ) in MM. Potential synergistic effects of DAC and JNJ in vitro were
assessed using the MM cell lines OPM-2 and 5T33MMvt. Proliferation and cell viability was time- and dose-dependently decreased upon treatment with DAC or JNJ. Moreover, treatment of cells with a combination of both agents synergistically decreased viability. For 5T33MMvt cells, JNJ alone or in combination with DAC induced a temporal G1-phase arrest followed by an increase of cells in subG1-phase in the combination group compared to single agent groups, while in the OPM-2 cells treatment resulted in a more prolonged G1-phase arrest. In agreement, the number of apoptotic MM cells was synergistically increased in the combination groups for both cell lines. Next, we tested also the potential anti-MM effect of DAC and JNJ in vivo, using the murine 5T33MM model. Combinatory treatment significantly decreased tumor burden and microvessel-density compared to single agent treatment. We conclude
that combination of the HDACi JNJ and the DNMTi DAC synergistically induce an anti-MM response.
Originele taal-2English
Pagina's (van-tot)111-111
Aantal pagina's1
TijdschriftHaematologica: the Haematology Journal
Volume96
Nummer van het tijdschrift2011
StatusPublished - 2 mei 2011
EvenementUnknown -
Duur: 2 mei 2011 → …

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