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Oncotarget. 2014 May 30;5(10):3168-72.

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

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1
Centre d'Immunologie de Marseille-Luminy, Aix-Marseille Université UM 2, 13288 Marseille, France.

Abstract

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.

PMID:
24930440
PMCID:
PMC4102800
DOI:
10.18632/oncotarget.1873
[Indexed for MEDLINE]
Free PMC Article

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