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. Gene expression was measured using Affymetrix platform in 4 distinct cell lines treated or untreated in vitro with Panobinostat at 5 nM for 24 hours. Four independent biological replicates were carried out.