The histone deacetylase inhibitor givinostat (ITF2357) exhibits potent anti-tumor activity against CRLF2-rearranged BCP-ALL.

We studied the in vitro and in vivo efficacy of the HDAC inhibitor Givinostat/ITF2357 in BCP-ALL with CRLF2 rearrangements. We used BCP-ALL CRLF2- rearranged MHH-CALL4 and MUTZ5 cell lines as well as blasts from CRLF2 rearranged BCP-ALL patients and patients’ derived xenograft samples. We conclude that Givinostat may represent a novel and effective tool, in combination with current chemotherapy, to treat this subsets of ALL with poor prognosis and chemotherapy-related toxicity. Gene expression was measured using Affymetrix platform in 5 pair of BCP-ALL patient derived xenograft samples treated or untreated ex vivo with Givinostat at 0.2 uM for 6 hours.