Publication: Therapeutic targeting of c-Myc in T-cell acute lymphoblastic leukemia, T-ALL.

Published in: Oncotarget 2014 May; 5(10): 3168-72

Authors: Loosveld M, Castellano R, Gon S, Goubard A, Crouzet T, Pouyet L, Prebet T, Vey N, Nadel B, Collette Y, Payet-Bornet D

Summary

T-ALL patients treated with intensive chemotherapy achieve high rates of remission. However, frequent long-term toxicities and relapses into chemotherapy-refractory tumors constitute major clinical challenges which could be met by targeted therapies. c-MYC is a central oncogene in T-ALL, prompting the exploration of the efficacy of MYC inhibitors such as JQ1 (BET-bromodomain inhibitor), and SAHA (HDAC inhibitor). Using a standardized ex vivo drug screening assay, we show here that JQ1 and SAHA show competitive efficiency compared to inhibitors of proteasome, PI3K/AKT/mTOR and NOTCH pathways, and synergize in combination with Vincristine. We also compared for the first time the in vivo relevance of such associations in mice xenografted with human primary T-ALLs. Our data indicate that although treatments combining JQ1 or SAHA with chemotherapeutic regimens might represent promising developments in T-ALL, combinations will need to be tailored to specific subgroups of responsive patients, the profiles of which still remain to be precisely defined.

Link to Pubmed [PMID] – 24930440