The HDAC inhibitor Panobinostat (LBH589) exerts in vivo anti-leukaemic activity against in MLL-rearranged Acute Lymphoblastic Leukaemia and involves the RNF20/RNF40/WAC H2B ubiquitination axis

We demonstrate the in vivo efficacy of the histone deacetylase inhibitor Panobinostat (LHB589) against MLL-rearranged ALL using xenograft mouse models of MLL-rearranged ALL cell lines and primary patient cells. Panobinostat monotherapy showed strong anti-leukaemic effects, extending survival and reducing overall disease burden. Comprehensive molecular analyses in vitro showed the anti-leukaemic activity in MLL-rearranged ALL to involve depletion of H2B ubiquitination via suppression of the RNF20/RNF40/WAC E3 ligase complex.

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Garrido Castro P, van Roon EHJ, Pinhanços SS, Trentin L, Schneider P, Kerstjens M, Te Kronnie G, Heidenreich O, Pieters R, Stam RW